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15476622 | Matrix metalloproteinase-1 promoter polymorphisms and changes in left ventricular volume following acute myocardial infarction. | The relation between matrix metalloproteinase-1 promoter genotype and remodeling was studied in 42 patients after their first acute myocardial infarctions. Patients possessing 2 GG alleles were at increased risk for remodeling compared with homozygotes for the G allele and heterozygotes possessing 1 G and 1 GG allele. | /"Matrix metalloproteinase-1"/ promoter polymorphisms and changes in left ventricular volume following acute /"myocardial infarction"/. | The relation between /"matrix metalloproteinase-1"/ promoter genotype and remodeling was studied in 42 patients after their first acute /"myocardial infarctions"/. Patients possessing 2 GG alleles were at increased risk for remodeling compared with homozygotes for the G allele and heterozygotes possessing 1 G and 1 GG allele. | [
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"entity_type": "Disease",
"text_name": "myocardial infarction"
},
{
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"end_idx": "282",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarctions"
},
{
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"end_idx": "26",
"entity_id": "4312",
"entity_type": "Gene",
"text_name": "Matrix metalloproteinase-1"
},
{
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"end_idx": "175",
"entity_id": "4312",
"entity_type": "Gene",
"text_name": "matrix metalloproteinase-1"
}
] | {
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"text_name": "Matrix metalloproteinase-1"
} | {
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"end_idx": "282",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarctions"
} | Yes |
15479186 | Haplotypic analyses of the aldosterone synthase gene CYP11B2 associated with stage-2 hypertension in northern Han Chinese. | The objective of this study was to investigate the association of polymorphisms in the aldosterone synthase gene CYP11B2 (-344T/C, Lys173/Arg, and an intronic conversion [IC]) with stage-2 hypertension in northern Han Chinese. A total of 503 hypertensives and their age-, gender-, and area-matched controls were included in this study. The female hypertensives had significantly higher frequencies of the -344T, 173Lys, and IC-conversion alleles (p = 0.002, 0.002, and 0.014, respectively). The estimated frequency of haplotype composed of the -344T, 173Lys, and IC-conversion alleles (haplotype 4) was significantly higher in the female hypertensives compared with their controls (p = 0.007). Using a multivariate score test, we found that haplotype 4 remained associated with female hypertension after the adjustment for covariates (p = 0.003), while the haplotype 3 of T-Arg-WT showed a protective effect both in the males and in the females (p = 0.03 and 0.006, respectively). The odds ratio for haplotype phase of 4-4 was 2.60 (95% CI, 1.21-5.58) and for 3-3, 0.20 (95% CI, 0.03-0.77). These results indicate that the Lys173 and the IC-conversion allele of the CYP11B2 gene confer an increased risk for stage-2 hypertension in northern Han Chinese women. | Haplotypic analyses of the /"aldosterone synthase"/ gene /"CYP11B2"/ associated with stage-2 /"hypertension"/ in northern Han Chinese. | The objective of this study was to investigate the association of polymorphisms in the /"aldosterone synthase"/ gene /"CYP11B2"/ (-344T/C, Lys173/Arg, and an intronic conversion [IC]) with stage-2 /"hypertension"/ in northern Han Chinese. A total of 503 /"hypertensives"/ and their age-, gender-, and area-matched controls were included in this study. The female /"hypertensives"/ had significantly higher frequencies of the -344T, 173Lys, and IC-conversion alleles (p = 0.002, 0.002, and 0.014, respectively). The estimated frequency of haplotype composed of the -344T, 173Lys, and IC-conversion alleles (haplotype 4) was significantly higher in the female /"hypertensives"/ compared with their controls (p = 0.007). Using a multivariate score test, we found that haplotype 4 remained associated with female /"hypertension"/ after the adjustment for covariates (p = 0.003), while the haplotype 3 of T-Arg-WT showed a protective effect both in the males and in the females (p = 0.03 and 0.006, respectively). The odds ratio for haplotype phase of 4-4 was 2.60 (95% CI, 1.21-5.58) and for 3-3, 0.20 (95% CI, 0.03-0.77). These results indicate that the Lys173 and the IC-conversion allele of the /"CYP11B2"/ gene confer an increased risk for stage-2 /"hypertension"/ in northern Han Chinese women. | [
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"text_name": "hypertension"
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"text_name": "aldosterone synthase"
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"entity_id": "1585",
"entity_type": "Gene",
"text_name": "CYP11B2"
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"entity_id": "1585",
"entity_type": "Gene",
"text_name": "aldosterone synthase"
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{
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"entity_id": "1585",
"entity_type": "Gene",
"text_name": "CYP11B2"
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"end_idx": "1296",
"entity_id": "1585",
"entity_type": "Gene",
"text_name": "CYP11B2"
}
] | {
"begin_idx": "27",
"end_idx": "47",
"entity_id": "1585",
"entity_type": "Gene",
"text_name": "aldosterone synthase"
} | {
"begin_idx": "365",
"end_idx": "378",
"entity_id": "D006973",
"entity_type": "Disease",
"text_name": "hypertensives"
} | Yes |
15522251 | Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele. | BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD. | Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for /"Alzheimer's disease"/: the effect of /"APOE"/ epsilon4 allele. | BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of /"Alzheimer's disease"/ (/"AD"/). Numerous lines of evidence have also suggested that individuals with at least one /"APOE"/ epsilon4 allele on chromosome 19 are at increased risk of developing /"AD"/. We tested these CSF markers in groups of subjects with /"AD"/ and healthy older control subjects, using the absence or presence of the /"APOE"/ epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of /"AD"/. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate /"AD"/), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of /"AD"/. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the /"APOE"/ epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an /"APOE"/ epsilon4 allele (p < .01). As expected, the /"AD"/ patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of /"APOE"/ epsilon4 allele and lower, more /"AD"/-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of /"AD"/. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to /"AD"/. | [
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"text_name": "cognitive abnormalities"
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{
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"entity_id": "348",
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] | {
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"entity_id": "348",
"entity_type": "Gene",
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} | {
"begin_idx": "77",
"end_idx": "96",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "Alzheimer's disease"
} | Yes |
15522251 | Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele. | BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD. | Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of /"APOE"/ epsilon4 allele. | BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one /"APOE"/ epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the /"APOE"/ epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the /"APOE"/ epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an /"APOE"/ epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of /"APOE"/ epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and /"cognitive abnormalities"/ with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD. | [
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"text_name": "AD"
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"end_idx": "1971",
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"text_name": "AD"
},
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"entity_id": "D003072",
"entity_type": "Disease",
"text_name": "cognitive abnormalities"
},
{
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},
{
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"entity_id": "348",
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}
] | {
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"entity_id": "348",
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"text_name": "APOE"
} | {
"begin_idx": "1704",
"end_idx": "1727",
"entity_id": "D003072",
"entity_type": "Disease",
"text_name": "cognitive abnormalities"
} | No |
15523642 | Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of NF1. | Nonsense, missense, and even silent mutation-associated exon skipping is recognized in an increasing number of genes as a novel form of splicing mutation. The analysis of individual mutations of this kind can shed light on basic pre-mRNA splicing mechanisms. Using cDNA-based mutation detection analysis, we have identified one missense and six nonsense mutations that lead to different extents of exon-lacking transcripts in neurofibromatosis type 1 (NF1) patients. We confirmed mutation-associated exon skipping in a heterologous hybrid minigene context. There is evidence that the disruption of functional exonic splicing enhancer (ESE) sequences is frequently the mechanism underlying mutation-associated exon skipping. Therefore, we examined the wild-type and mutant NF1 sequences with two available ESE-prediction programs. Either or both programs predicted the disruption of ESE motifs in six out of the seven analyzed mutations. To ascertain the function of the predicted ESEs, we quantitatively measured their ability to rescue splicing of an enhancer-dependent exon, and found that all seven mutant ESEs had reduced splicing enhancement activity compared to the wild-type sequences. Our results suggest that the wild-type sequences function as ESE elements, whose disruption is responsible for the mutation-associated exon skipping observed in the NF1 patients. Further, this study illustrates the utility of ESE-prediction programs for delineating candidate sequences that may serve as ESE elements. However, until more refined prediction algorithms have been developed, experimental data, preferably from patient tissues, remain indispensable to assess the clinical significance, particularly of missense and silent mutations, and to understand the structure-function relationship in the corresponding protein. | Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of /"NF1"/F1"/. | Nonsense, missense, and even silent mutation-associated exon skipping is recognized in an increasing number of genes as a novel form of splicing mutation. The analysis of individual mutations of this kind can shed light on basic pre-mRNA splicing mechanisms. Using cDNA-based mutation detection analysis, we have identified one missense and six nonsense mutations that lead to different extents of exon-lacking transcripts in /"neurofibromatosis type 1"/ 1"/ (/"NF1"/F1"/) patients. We confirmed mutation-associated exon skipping in a heterologous hybrid minigene context. There is evidence that the disruption of functional exonic splicing enhancer (ESE) sequences is frequently the mechanism underlying mutation-associated exon skipping. Therefore, we examined the wild-type and mutant /"NF1"/F1"/ sequences with two available ESE-prediction programs. Either or both programs predicted the disruption of ESE motifs in six out of the seven analyzed mutations. To ascertain the function of the predicted ESEs, we quantitatively measured their ability to rescue splicing of an enhancer-dependent exon, and found that all seven mutant ESEs had reduced splicing enhancement activity compared to the wild-type sequences. Our results suggest that the wild-type sequences function as ESE elements, whose disruption is responsible for the mutation-associated exon skipping observed in the /"NF1"/F1"/ patients. Further, this study illustrates the utility of ESE-prediction programs for delineating candidate sequences that may serve as ESE elements. However, until more refined prediction algorithms have been developed, experimental data, preferably from patient tissues, remain indispensable to assess the clinical significance, particularly of missense and silent mutations, and to understand the structure-function relationship in the corresponding protein. | [
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"text_name": "NF1"
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}
] | {
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} | {
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"entity_id": "D009456",
"entity_type": "Disease",
"text_name": "neurofibromatosis type 1"
} | Yes |
15562935 | An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease. | BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is the major receptor of oxidized LDL in endothelial cells. The expression of LOX-1 was shown to be upregulated in atherosclerotic lesions. Recently, LOX-1 gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the association between this polymorphism and coronary artery disease (CAD). METHODS: We evaluated LOX-1 gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. RESULTS: Study patients were categorized into three groups: normal/minimal stenosis (< or =25%) (n = 128); mild stenosis (26-50%) (n = 39); and significant stenosis (>50%) (n = 419). Of the 419 patients with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of LOX- 1 gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01). The frequency of LOX-1 gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of CAD: 49% in normal/minimal stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated LOX-1 gene variants to be inversely associated with the presence of significant stenosis (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The LOX-1 gene variants at 501 were found to be inversely associated with the severity of CAD. This polymorphism may be modifying the severity of CAD. | An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of /"coronary artery disease"/. | BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (/"LOX-1"/) is the major receptor of oxidized LDL in endothelial cells. The expression of /"LOX-1"/ was shown to be upregulated in atherosclerotic lesions. Recently, /"LOX-1"/ gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the association between this polymorphism and /"coronary artery disease"/ (/"CAD"/). METHODS: We evaluated /"LOX-1"/ gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. RESULTS: Study patients were categorized into three groups: normal/minimal stenosis (< or =25%) (n = 128); mild stenosis (26-50%) (n = 39); and significant stenosis (>50%) (n = 419). Of the 419 patients with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of /"LOX- 1"/ gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01). The frequency of /"LOX-1"/ gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of /"CAD"/: 49% in normal/minimal stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated /"LOX-1"/ gene variants to be inversely associated with the presence of significant stenosis (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The /"LOX-1"/ gene variants at 501 were found to be inversely associated with the severity of /"CAD"/. This polymorphism may be modifying the severity of /"CAD"/. | [
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"entity_type": "Disease",
"text_name": "coronary artery disease"
} | Yes |
15562935 | An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease. | BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is the major receptor of oxidized LDL in endothelial cells. The expression of LOX-1 was shown to be upregulated in atherosclerotic lesions. Recently, LOX-1 gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the association between this polymorphism and coronary artery disease (CAD). METHODS: We evaluated LOX-1 gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. RESULTS: Study patients were categorized into three groups: normal/minimal stenosis (< or =25%) (n = 128); mild stenosis (26-50%) (n = 39); and significant stenosis (>50%) (n = 419). Of the 419 patients with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of LOX- 1 gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01). The frequency of LOX-1 gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of CAD: 49% in normal/minimal stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated LOX-1 gene variants to be inversely associated with the presence of significant stenosis (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The LOX-1 gene variants at 501 were found to be inversely associated with the severity of CAD. This polymorphism may be modifying the severity of CAD. | An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease. | BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (/"LOX-1"/) is the major receptor of oxidized LDL in endothelial cells. The expression of /"LOX-1"/ was shown to be upregulated in atherosclerotic lesions. Recently, /"LOX-1"/ gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the association between this polymorphism and coronary artery disease (CAD). METHODS: We evaluated /"LOX-1"/ gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. RESULTS: Study patients were categorized into three groups: normal/minimal /"stenosis"/ (< or =25%) (n = 128); mild /"stenosis"/ (26-50%) (n = 39); and significant /"stenosis"/ (>50%) (n = 419). Of the 419 patients with significant /"stenosis"/, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of /"LOX- 1"/ gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal /"stenosis"/ (36 vs. 49%, p < 0.01). The frequency of /"LOX-1"/ gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of CAD: 49% in normal/minimal /"stenosis"/, 41% in mild /"stenosis"/, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated /"LOX-1"/ gene variants to be inversely associated with the presence of significant /"stenosis"/ (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The /"LOX-1"/ gene variants at 501 were found to be inversely associated with the severity of CAD. This polymorphism may be modifying the severity of CAD. | [
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15571962 | BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | BRCA2, but not /"BRCA1"/, mutations account for /"familial ovarian cancer"/ in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the /"BRCA1"/ G5193A and BRCA2 999del5 mutations in all /"ovarian cancer"/ patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, /"BRCA1"/ and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing /"ovarian cancer"/ was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of /"ovarian cancer"/ cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The /"BRCA1"/ G5193A mutation is too rare to contribute significantly to /"ovarian cancer"/ in Iceland. | [
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"entity_id": "D010051",
"entity_type": "Disease",
"text_name": "familial ovarian cancer"
} | Yes |
15571962 | BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | /"BRCA2"/, but not BRCA1, mutations account for /"familial ovarian cancer"/ in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and /"BRCA2"/ 999del5 mutations in all /"ovarian cancer"/ patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and /"BRCA2"/ mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing /"ovarian cancer"/ was 20.65 for /"BRCA2"/ carriers. Family history of breast/ovarian cancer was present for 70% of /"BRCA2"/ carriers and approximately 14% for non-carriers with carcinoma. In conclusion, /"BRCA2"/ 999del5 is present in 6% of /"ovarian cancer"/ cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to /"ovarian cancer"/ in Iceland. | [
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15571962 | BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | BRCA2, but not /"BRCA1"/, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the /"BRCA1"/ G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 /"carcinomas"/ and 74 borderline tumours) were available. In the /"carcinomas"/, /"BRCA1"/ and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with /"carcinoma"/. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The /"BRCA1"/ G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | [
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15571962 | BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | /"BRCA2"/, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and /"BRCA2"/ 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 /"carcinomas"/ and 74 borderline tumours) were available. In the /"carcinomas"/, BRCA1 and /"BRCA2"/ mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for /"BRCA2"/ carriers. Family history of breast/ovarian cancer was present for 70% of /"BRCA2"/ carriers and approximately 14% for non-carriers with /"carcinoma"/. In conclusion, /"BRCA2"/ 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland. | [
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15583997 | [Association of the T(-344)C polymorphism of aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh isolated group]. | OBJECTIVE: To investigate the association of the T(-344)C polymorphism of aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh isolated population. METHODS: The study covered 186 hypertensives and 168 normotensive controls in Xinjiang Kazakh population. The segment of CYP11B2 was amplified from DNA by polymerase chain reaction(PCR). The PCR products were digested by restriction endonuclease. RESULTS: The frequencies of C and T in hypertensive group (0.45 and 0.55) were not significantly different from those in the control group (0.43 and 0.57; chi-square test=0.380, P=0.537). The frequencies of CYP11B2 genotypes of CC, CT and TT were 0.20, 0.50 and 0.30 in hypertensives respectively, and 0.12, 0.61 and 0.27 in controls respectively. There was no significant difference in genotypes between hypertensive group and normotensive group (chi-square test=4.838, P=0.089). But the frequencies of CC genotype were higher in the female hypertensives than in the normotensive controls (chi-square test=6.104, P<0.05). CONCLUSION: The results suggested that the T(-344)C polymorphism of CYP11B2 gene may be associated with hypertension in female Kazakh population of Xinjiang Barlikun area. | [Association of the T(-344)C polymorphism of /"aldosterone synthase"/ gene /"CYP11B2"/ with essential /"hypertension"/ in Xinjiang Kazakh isolated group]. | OBJECTIVE: To investigate the association of the T(-344)C polymorphism of /"aldosterone synthase"/ gene /"CYP11B2"/ with essential /"hypertension"/ in Xinjiang Kazakh isolated population. METHODS: The study covered 186 /"hypertensives"/ and 168 normotensive controls in Xinjiang Kazakh population. The segment of /"CYP11B2"/ was amplified from DNA by polymerase chain reaction(PCR). The PCR products were digested by restriction endonuclease. RESULTS: The frequencies of C and T in /"hypertensive"/ group (0.45 and 0.55) were not significantly different from those in the control group (0.43 and 0.57; chi-square test=0.380, P=0.537). The frequencies of /"CYP11B2"/ genotypes of CC, CT and TT were 0.20, 0.50 and 0.30 in /"hypertensives"/ respectively, and 0.12, 0.61 and 0.27 in controls respectively. There was no significant difference in genotypes between /"hypertensive"/ group and normotensive group (chi-square test=4.838, P=0.089). But the frequencies of CC genotype were higher in the female /"hypertensives"/ than in the normotensive controls (chi-square test=6.104, P<0.05). CONCLUSION: The results suggested that the T(-344)C polymorphism of /"CYP11B2"/ gene may be associated with /"hypertension"/ in female Kazakh population of Xinjiang Barlikun area. | [
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15609125 | Integrin beta3 Leu33Pro polymorphism and breast cancer risk: a population-based case-control study in Germany. | A functional polymorphism at codon 33 (leucine-to-proline, Leu33Pro)/nucleotide 1565 (T-to-C, T1565C) of the integrin beta3 has been hypothesized to increase the risk of breast cancer and its metastasis. Three studies have been conducted up to date and the results were contradictory. We used a large population-based age-matched case-control study in German Caucasian women by the age of 50 years to assess breast cancer risk associated with this polymorphism, taking into consideration of possible interaction with other risk factors, and to examine if it affects clinical presentation. Overall, the odds ratios (OR) for breast cancer were not increased in women carrying either allele. However, we observed a differential effect of the Leu33Pro polymorphism by age group when patients were stratified by 45 years of age (p=0.055). Being a carrier of the 33proline allele was found to be associated with a 32% increased risk (95% Cl=1.0-1.8) for breast cancer compared to the wild-type leucine homozygotes among women age 45 or younger but not in older women. Furthermore, we observed significant dose effect of the 33proline allele (p=0.04), with 30% risk increase per allele (95% Cl=1.0-1.7). Significant evidence was also found for a positive association between 33proline carrier status and increasing axillary node involvement (p=0.048) but neither size nor grading of tumor in this study. Our data suggest that inheritance of the integrin beta3 Leu33Pro polymorphism may increase the breast cancer risk by age 45 in the German population. | /"Integrin beta3"/ Leu33Pro polymorphism and /"breast cancer"/ risk: a population-based case-control study in Germany. | A functional polymorphism at codon 33 (leucine-to-proline, Leu33Pro)/nucleotide 1565 (T-to-C, T1565C) of the /"integrin beta3"/ has been hypothesized to increase the risk of /"breast cancer"/ and its metastasis. Three studies have been conducted up to date and the results were contradictory. We used a large population-based age-matched case-control study in German Caucasian women by the age of 50 years to assess /"breast cancer"/ risk associated with this polymorphism, taking into consideration of possible interaction with other risk factors, and to examine if it affects clinical presentation. Overall, the odds ratios (OR) for /"breast cancer"/ were not increased in women carrying either allele. However, we observed a differential effect of the Leu33Pro polymorphism by age group when patients were stratified by 45 years of age (p=0.055). Being a carrier of the 33proline allele was found to be associated with a 32% increased risk (95% Cl=1.0-1.8) for /"breast cancer"/ compared to the wild-type leucine homozygotes among women age 45 or younger but not in older women. Furthermore, we observed significant dose effect of the 33proline allele (p=0.04), with 30% risk increase per allele (95% Cl=1.0-1.7). Significant evidence was also found for a positive association between 33proline carrier status and increasing axillary node involvement (p=0.048) but neither size nor grading of tumor in this study. Our data suggest that inheritance of the /"integrin beta3"/ Leu33Pro polymorphism may increase the /"breast cancer"/ risk by age 45 in the German population. | [
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15609125 | Integrin beta3 Leu33Pro polymorphism and breast cancer risk: a population-based case-control study in Germany. | A functional polymorphism at codon 33 (leucine-to-proline, Leu33Pro)/nucleotide 1565 (T-to-C, T1565C) of the integrin beta3 has been hypothesized to increase the risk of breast cancer and its metastasis. Three studies have been conducted up to date and the results were contradictory. We used a large population-based age-matched case-control study in German Caucasian women by the age of 50 years to assess breast cancer risk associated with this polymorphism, taking into consideration of possible interaction with other risk factors, and to examine if it affects clinical presentation. Overall, the odds ratios (OR) for breast cancer were not increased in women carrying either allele. However, we observed a differential effect of the Leu33Pro polymorphism by age group when patients were stratified by 45 years of age (p=0.055). Being a carrier of the 33proline allele was found to be associated with a 32% increased risk (95% Cl=1.0-1.8) for breast cancer compared to the wild-type leucine homozygotes among women age 45 or younger but not in older women. Furthermore, we observed significant dose effect of the 33proline allele (p=0.04), with 30% risk increase per allele (95% Cl=1.0-1.7). Significant evidence was also found for a positive association between 33proline carrier status and increasing axillary node involvement (p=0.048) but neither size nor grading of tumor in this study. Our data suggest that inheritance of the integrin beta3 Leu33Pro polymorphism may increase the breast cancer risk by age 45 in the German population. | /"Integrin beta3"/ Leu33Pro polymorphism and breast cancer risk: a population-based case-control study in Germany. | A functional polymorphism at codon 33 (leucine-to-proline, Leu33Pro)/nucleotide 1565 (T-to-C, T1565C) of the /"integrin beta3"/ has been hypothesized to increase the risk of breast cancer and its /"metastasis"/. Three studies have been conducted up to date and the results were contradictory. We used a large population-based age-matched case-control study in German Caucasian women by the age of 50 years to assess breast cancer risk associated with this polymorphism, taking into consideration of possible interaction with other risk factors, and to examine if it affects clinical presentation. Overall, the odds ratios (OR) for breast cancer were not increased in women carrying either allele. However, we observed a differential effect of the Leu33Pro polymorphism by age group when patients were stratified by 45 years of age (p=0.055). Being a carrier of the 33proline allele was found to be associated with a 32% increased risk (95% Cl=1.0-1.8) for breast cancer compared to the wild-type leucine homozygotes among women age 45 or younger but not in older women. Furthermore, we observed significant dose effect of the 33proline allele (p=0.04), with 30% risk increase per allele (95% Cl=1.0-1.7). Significant evidence was also found for a positive association between 33proline carrier status and increasing axillary node involvement (p=0.048) but neither size nor grading of tumor in this study. Our data suggest that inheritance of the /"integrin beta3"/ Leu33Pro polymorphism may increase the breast cancer risk by age 45 in the German population. | [
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15624175 | Genotyping the -6A/G functional polymorphism in the core promoter region of angiotensinogen gene by microchip electrophoresis. | Angiotensinogen (AGT) gene has been regarded as one of the candidate genes for essential hypertension. In our study, the role of AGT gene as a putatively predisposing gene for hypertension was evaluated by genotyping a A (-6) G polymorphism in the core promoter region in 123 patients with essential hypertension and 103 healthy controls. A microchip electrophoresis method coupled with polymorphism chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay was used for genotyping the A (-6) G single-nucleotide polymorphism. The separation and detection of the digested PCR amplicons were completed just in 280 s or less. The genotype frequency fulfilled the criteria of the Hardy-Weinbery equilibrium (X2 = 3.067, P > 0.05). The results showed a higher frequency of the -6 A allele (0.70) in the normotensive subjects, which is higher than those reported in Germany (0.47) and Czech (0.40) populations, but similar to that found in Japanese populations (0.73). The frequencies of genotype AA, AG, and GG were 0.46, 0.49, and 0.05 in hypertensive subjects, and 0.44, 0.53, and 0.03 in control subjects. There is no significant difference in the distributions of the genotype and allele between the two groups (X2 = 0.88, P > 0.05; X2 = 0.024, P > 0.05). These findings differ from some of the results obtained in other ethnic groups, indicating the potential importance of ethnic origin in the assessment of genetic risk identifiers for a complex disease. | Genotyping the -6A/G functional polymorphism in the core promoter region of /"angiotensinogen"/ gene by microchip electrophoresis. | /"Angiotensinogen"/ (/"AGT"/) gene has been regarded as one of the candidate genes for essential /"hypertension"/. In our study, the role of /"AGT"/ gene as a putatively predisposing gene for /"hypertension"/ was evaluated by genotyping a A (-6) G polymorphism in the core promoter region in 123 patients with essential /"hypertension"/ and 103 healthy controls. A microchip electrophoresis method coupled with polymorphism chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay was used for genotyping the A (-6) G single-nucleotide polymorphism. The separation and detection of the digested PCR amplicons were completed just in 280 s or less. The genotype frequency fulfilled the criteria of the Hardy-Weinbery equilibrium (X2 = 3.067, P > 0.05). The results showed a higher frequency of the -6 A allele (0.70) in the normotensive subjects, which is higher than those reported in Germany (0.47) and Czech (0.40) populations, but similar to that found in Japanese populations (0.73). The frequencies of genotype AA, AG, and GG were 0.46, 0.49, and 0.05 in /"hypertensive"/ subjects, and 0.44, 0.53, and 0.03 in control subjects. There is no significant difference in the distributions of the genotype and allele between the two groups (X2 = 0.88, P > 0.05; X2 = 0.024, P > 0.05). These findings differ from some of the results obtained in other ethnic groups, indicating the potential importance of ethnic origin in the assessment of genetic risk identifiers for a complex disease. | [
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15635591 | Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease. | The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of PD. When the GG genotypes of the IL-6 and ERbeta SNPs were combined, the combination was much more robustly associated with PD, and especially with PD with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing PD, particularly regarding early age of onset PD, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene. | Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to /"Parkinson's disease"/. | The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with /"Parkinson's disease"/ (/"PD"/). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (/"ERbeta"/) and age of onset of /"PD"/. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the /"ERbeta"/ G-1730A SNP on the risk for /"PD"/, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with /"PD"/ and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of /"PD"/. When the GG genotypes of the IL-6 and /"ERbeta"/ SNPs were combined, the combination was much more robustly associated with /"PD"/, and especially with /"PD"/ with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing /"PD"/, particularly regarding early age of onset /"PD"/, and that the effect is modified by interaction of the G-1730A SNP in the /"ERbeta"/ gene. | [
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15635591 | Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease. | The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of PD. When the GG genotypes of the IL-6 and ERbeta SNPs were combined, the combination was much more robustly associated with PD, and especially with PD with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing PD, particularly regarding early age of onset PD, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene. | Interaction of polymorphisms in the genes encoding /"interleukin-6"/ and estrogen receptor beta on the susceptibility to /"Parkinson's disease"/. | The multifunctional cytokine /"interleukin-6"/ (/"IL-6"/) is involved in inflammatory processes in the central nervous system and increased levels of /"IL-6"/ have been found in patients with /"Parkinson's disease"/ (/"PD"/). It is known that estrogen inhibits the production of /"IL-6"/, via action on estrogen receptors, thereby pointing to an important influence of estrogen on /"IL-6"/. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of /"PD"/. To investigate the influence of a G/C SNP at position 174 in the promoter of the /"IL-6"/ gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for /"PD"/, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with /"PD"/ and 308 controls. A significantly elevated frequency of the GG genotype of the /"IL-6"/ SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of /"PD"/. When the GG genotypes of the /"IL-6"/ and ERbeta SNPs were combined, the combination was much more robustly associated with /"PD"/, and especially with /"PD"/ with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the /"IL-6"/ promoter may influence the risk for developing /"PD"/, particularly regarding early age of onset /"PD"/, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene. | [
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15649153 | CTLA4 polymorphisms are associated with vitiligo, in patients with concomitant autoimmune diseases. | The cytotoxic T lymphocyte antigen4 (CTLA4) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the CTLA4 gene and autoimmune disorders, but no study has as yet found any definite association between vitiligo and the CTLA4 polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble CTLA4. To assess these new polymorphisms in patients with vitiligo, we genotyped 100 vitiligo patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with isolated vitiligo, but a significant association was seen in patients with vitiligo and other autoimmune diseases. The results indicate that the polymorphisms in the CTLA4 gene region confer susceptibility to vitiligo when occurring together with other autoimmune diseases, but not in patients with isolated vitiligo. This raises the possibility that there are two distinct forms of vitiligo where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes. | /"CTLA4"/ polymorphisms are associated with vitiligo, in patients with concomitant /"autoimmune diseases"/. | The /"cytotoxic T lymphocyte antigen4"/ (/"CTLA4"/) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the /"CTLA4"/ gene and /"autoimmune disorders"/, but no study has as yet found any definite association between vitiligo and the /"CTLA4"/ polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble /"CTLA4"/. To assess these new polymorphisms in patients with vitiligo, we genotyped 100 vitiligo patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with isolated vitiligo, but a significant association was seen in patients with vitiligo and other /"autoimmune diseases"/. The results indicate that the polymorphisms in the /"CTLA4"/ gene region confer susceptibility to vitiligo when occurring together with other /"autoimmune diseases"/, but not in patients with isolated vitiligo. This raises the possibility that there are two distinct forms of vitiligo where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes. | [
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15649153 | CTLA4 polymorphisms are associated with vitiligo, in patients with concomitant autoimmune diseases. | The cytotoxic T lymphocyte antigen4 (CTLA4) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the CTLA4 gene and autoimmune disorders, but no study has as yet found any definite association between vitiligo and the CTLA4 polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble CTLA4. To assess these new polymorphisms in patients with vitiligo, we genotyped 100 vitiligo patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with isolated vitiligo, but a significant association was seen in patients with vitiligo and other autoimmune diseases. The results indicate that the polymorphisms in the CTLA4 gene region confer susceptibility to vitiligo when occurring together with other autoimmune diseases, but not in patients with isolated vitiligo. This raises the possibility that there are two distinct forms of vitiligo where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes. | /"CTLA4"/ polymorphisms are associated with /"vitiligo"/, in patients with concomitant autoimmune diseases. | The /"cytotoxic T lymphocyte antigen4"/ (/"CTLA4"/) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the /"CTLA4"/ gene and autoimmune disorders, but no study has as yet found any definite association between /"vitiligo"/ and the /"CTLA4"/ polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble /"CTLA4"/. To assess these new polymorphisms in patients with /"vitiligo"/, we genotyped 100 /"vitiligo"/ patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with /"isolated vitiligo"/, but a significant association was seen in patients with /"vitiligo"/ and other autoimmune diseases. The results indicate that the polymorphisms in the /"CTLA4"/ gene region confer susceptibility to /"vitiligo"/ when occurring together with other autoimmune diseases, but not in patients with /"isolated vitiligo"/. This raises the possibility that there are two distinct forms of /"vitiligo"/ where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes. | [
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15659127 | Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | Angiotensinogen and /"plasminogen activator inhibitor-1"/ gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that /"plasminogen activator inhibitor-1"/ (/"PAI-1"/) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and /"PAI-1"/ genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for /"PAI-1"/ polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and /"PAI-1"/ genotypes prior to transplantation may help identify patients who at risk for /"chronic renal transplant dysfunction"/. | [
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15659127 | Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | /"Angiotensinogen"/ and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between /"angiotensinogen"/ (/"AGT"/) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for /"AGT"/ polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of /"AGT"/ M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for /"chronic renal transplant dysfunction"/. | [
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15659127 | Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | /"Angiotensinogen"/ and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | /"Chronic allograft dysfunction"/ (/"CAD"/) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between /"angiotensinogen"/ (/"AGT"/) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and /"CAD"/ assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for /"AGT"/ polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with /"CAD"/ had significantly lower frequencies of the MM genotype and the M allele than the recipients without /"CAD"/ (p < 0.05 and <0.001). The transplant recipients with /"CAD"/ also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without /"CAD"/ (p < 0.001 and <0.05). Determination of /"AGT"/ M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | [
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15659127 | Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | /"Angiotensinogen"/ and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. | /"Chronic allograft dysfunction"/ (/"CAD"/) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between /"angiotensinogen"/ (/"AGT"/) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and /"CAD"/ assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for /"AGT"/ polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with /"CAD"/ had significantly lower frequencies of the MM genotype and the M allele than the recipients without /"CAD"/ (p < 0.05 and <0.001). The transplant recipients with /"CAD"/ also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without /"CAD"/ (p < 0.001 and <0.05). Determination of /"AGT"/ M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. | [
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15660776 | ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy. | PURPOSE: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE. | /"ApoE"/ epsilon4 allele and disease duration affect verbal learning in mild /"temporal lobe epilepsy"/. | PURPOSE: To clarify the possible role of other factors including the /"ApoE"/ epsilon4 allele for memory decline in /"temporal lobe epilepsy"/ (/"TLE"/). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional /"TLE"/, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an /"ApoE"/ epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the /"ApoE"/ genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the /"ApoE"/ epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in /"TLE"/. | [
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"text_name": "temporal lobe epilepsy"
} | Yes |
15660776 | ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy. | PURPOSE: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE. | /"ApoE"/ epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy. | PURPOSE: To clarify the possible role of other factors including the /"ApoE"/ epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating /"verbal learning deficit"/ (/"VLD"/). The presence of an /"ApoE"/ epsilon4 allele was associated with an increased risk of /"VLD"/ (OR, 4.18; 95% CI, 1.66-10.55). The effect of the /"ApoE"/ genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with /"VLD"/ (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the /"ApoE"/ epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE. | [
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} | No |
15670652 | Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease. | It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association. | Australian data and meta-analysis lend support for /"alpha-synuclein"/ (NACP-Rep1) as a risk factor for /"Parkinson's disease"/. | It remains unclear whether genetic variants in /"SNCA"/ (the /"alpha-synuclein"/ gene) alter risk for sporadic /"Parkinson's disease"/ (/"PD"/). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of /"SNCA"/ has been previously examined as a potential susceptibility factor for /"PD"/ with conflicting results. We report genotype and allele distributions at this locus from 369 /"PD"/ cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for /"PD"/ (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association. | [
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"text_name": "Parkinson's disease"
} | Yes |
15670652 | Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease. | It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association. | Australian data and meta-analysis lend support for alpha-synuclein (NACP-/"Rep1"/) as a risk factor for /"Parkinson's disease"/. | It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic /"Parkinson's disease"/ (/"PD"/). The polymorphic mixed sequence repeat (NACP-/"Rep1"/) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for /"PD"/ with conflicting results. We report genotype and allele distributions at this locus from 369 /"PD"/ cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European /"Rep1"/ data yielded a highly significant association between the 0 allele and a reduced risk for /"PD"/ (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association. | [
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"text_name": "Rep1"
} | {
"begin_idx": "497",
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"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
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15675129 | Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the interferon gamma (IFN-gamma) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of IFN-gamma gene. RESULTS: No significant differences in the distribution of alleles for the IFN-gamma gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of IFN-gamma allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of IFN-gamma allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, IFN-gamma functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | /"Interferon-gamma"/ gene microsatellite polymorphisms in patients with biopsy-proven /"giant cell arteritis"/ and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of /"giant cell arteritis"/ (/"GCA"/) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the /"interferon gamma (IFN-gamma"/) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven /"GCA"/ patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of /"IFN-gamma"/ gene. RESULTS: No significant differences in the distribution of alleles for the /"IFN-gamma"/ gene polymorphism between /"GCA"/ and isolated PMR patients and controls were found. However, the frequency of /"IFN-gamma"/ allele *4 (128 bp) was reduced in /"GCA"/ patients (33.1%) compared with isolated PMR patients (46.2%). Also, /"GCA"/ patients with visual ischemic manifestations exhibited a significantly reduced frequency of /"IFN-gamma"/ allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the /"GCA"/ patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining /"GCA"/ patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In /"GCA"/, /"IFN-gamma"/ functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | [
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} | {
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"entity_id": "D013700",
"entity_type": "Disease",
"text_name": "giant cell arteritis"
} | Yes |
15675129 | Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the interferon gamma (IFN-gamma) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of IFN-gamma gene. RESULTS: No significant differences in the distribution of alleles for the IFN-gamma gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of IFN-gamma allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of IFN-gamma allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, IFN-gamma functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | /"Interferon-gamma"/ gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated /"polymyalgia rheumatica"/. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and /"polymyalgia rheumatica"/ (/"PMR"/). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the /"interferon gamma (IFN-gamma"/) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with /"isolated PMR"/, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of /"IFN-gamma"/ gene. RESULTS: No significant differences in the distribution of alleles for the /"IFN-gamma"/ gene polymorphism between GCA and /"isolated PMR"/ patients and controls were found. However, the frequency of /"IFN-gamma"/ allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with /"isolated PMR"/ patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of /"IFN-gamma"/ allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, /"IFN-gamma"/ functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | [
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} | Yes |
15675129 | Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the interferon gamma (IFN-gamma) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of IFN-gamma gene. RESULTS: No significant differences in the distribution of alleles for the IFN-gamma gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of IFN-gamma allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of IFN-gamma allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, IFN-gamma functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | /"Interferon-gamma"/ gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the /"interferon gamma (IFN-gamma"/) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of /"IFN-gamma"/ gene. RESULTS: No significant differences in the distribution of alleles for the /"IFN-gamma"/ gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of /"IFN-gamma"/ allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with /"visual ischemic"/ manifestations exhibited a significantly reduced frequency of /"IFN-gamma"/ allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with /"visual ischemic"/ manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, /"IFN-gamma"/ functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | [
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} | No |
15675129 | Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the interferon gamma (IFN-gamma) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of IFN-gamma gene. RESULTS: No significant differences in the distribution of alleles for the IFN-gamma gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of IFN-gamma allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of IFN-gamma allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, IFN-gamma functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | /"Interferon-gamma"/ gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. | OBJECTIVES: Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the /"interferon gamma (IFN-gamma"/) gene with disease susceptibility and clinical expression of these conditions. METHODS: Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of /"IFN-gamma"/ gene. RESULTS: No significant differences in the distribution of alleles for the /"IFN-gamma"/ gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of /"IFN-gamma"/ allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with /"visual ischemic"/ manifestations exhibited a significantly reduced frequency of /"IFN-gamma"/ allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13-1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with /"visual ischemic"/ manifestations (71.4% versus 44.4% in the remaining GCA patients; p = 0.01 [OR = 3.13, 95% CI: 1.27-7.68]). CONCLUSIONS: In GCA, /"IFN-gamma"/ functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis. | [
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} | No |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in /"cystic fibrosis"/ patients with class 1 or 2 /"CFTR"/ mutations. | BACKGROUND: Most /"cystic fibrosis"/ (/"CF"/) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to /"CF"/ genotype. We assessed the decline of pancreatic function in /"CF"/ infants carrying class 1 or 2 /"CFTR"/ mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight /"CF"/ patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all /"CF"/ patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened /"CF"/ subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: /"CF"/ patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 /"CFTR"/ mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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"entity_id": "D003550",
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"text_name": "cystic fibrosis"
} | Yes |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 /"CFTR"/ mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop /"steatorrhea"/ and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 /"CFTR"/ mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. /"Steatorrhea"/ was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 /"CFTR"/ mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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] | {
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} | {
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"entity_id": "D045602",
"entity_type": "Disease",
"text_name": "steatorrhea"
} | Yes |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 /"CFTR"/ mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 /"CFTR"/ mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved /"pancreatic insufficiency"/ in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 /"CFTR"/ mutations, /"pancreatic insufficiency"/ develops in the first months of life. The proper assessment of /"pancreatic insufficiency"/ and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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}
] | {
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} | {
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"entity_id": "D010188",
"entity_type": "Disease",
"text_name": "pancreatic insufficiency"
} | Yes |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal /"pancreatic elastase-1"/ concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal /"pancreatic elastase-1"/ concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal /"pancreatic elastase-1"/ concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved /"pancreatic insufficiency"/ in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, /"pancreatic insufficiency"/ develops in the first months of life. The proper assessment of /"pancreatic insufficiency"/ and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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] | {
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"entity_id": "1990",
"entity_type": "Gene",
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} | {
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"entity_type": "Disease",
"text_name": "pancreatic insufficiency"
} | No |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal /"pancreatic elastase-1"/ concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal /"pancreatic elastase-1"/ concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal /"pancreatic elastase-1"/ concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved /"pancreatic insufficiency"/ in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, /"pancreatic insufficiency"/ develops in the first months of life. The proper assessment of /"pancreatic insufficiency"/ and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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"text_name": "pancreatic elastase-1"
} | {
"begin_idx": "1578",
"end_idx": "1602",
"entity_id": "D010188",
"entity_type": "Disease",
"text_name": "pancreatic insufficiency"
} | No |
15699697 | Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | Early decline of pancreatic function in /"cystic fibrosis"/ patients with class 1 or 2 CFTR mutations. | BACKGROUND: Most /"cystic fibrosis"/ (/"CF"/) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to /"CF"/ genotype. We assessed the decline of pancreatic function in /"CF"/ infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight /"CF"/ patients were included in the study and 27 completed the study. In all subjects, fecal /"pancreatic elastase-1"/ concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all /"CF"/ patients, fecal /"pancreatic elastase-1"/ concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened /"CF"/ subjects had fecal /"pancreatic elastase-1"/ concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: /"CF"/ patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes. | [
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15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, /"CAT"/) and survival after treatment for /"breast cancer"/. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for /"breast cancer"/ and improve survival. Women who were treated with radiation and/or chemotherapy for incident /"breast cancer"/ at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, /"CAT"/, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both /"CAT"/ TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for /"breast cancer"/. | [
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15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (MPO, /"MnSOD"/, CAT) and survival after treatment for /"breast cancer"/. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for /"breast cancer"/ and improve survival. Women who were treated with radiation and/or chemotherapy for incident /"breast cancer"/ at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and /"MnSOD"/, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and /"MnSOD"/ CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for /"MnSOD"/ and MPO, women with /"MnSOD"/ CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for /"breast cancer"/. | [
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15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (/"MPO"/, MnSOD, CAT) and survival after treatment for /"breast cancer"/. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and /"myeloperoxidase"/ converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for /"breast cancer"/ and improve survival. Women who were treated with radiation and/or chemotherapy for incident /"breast cancer"/ at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and /"MPO"/ genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for /"MPO"/ G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and /"MPO"/, women with MnSOD CC and /"MPO"/ GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for /"breast cancer"/. | [
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15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (MPO, /"MnSOD"/, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell /"death"/ by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and /"MnSOD"/, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and /"MnSOD"/ CC genotypes were associated with nonsignificant reduced hazard of /"death"/. When we combined genotypes associated with higher levels of reactive oxygen species for /"MnSOD"/ and MPO, women with /"MnSOD"/ CC and MPO GG genotypes had a 3-fold decrease in hazard of /"death"/ (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | [
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15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, /"CAT"/) and survival after treatment for breast cancer. | The proximate cause of /"cancer"/ cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, /"CAT"/, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both /"CAT"/ TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | [
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} | No |
15705913 | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer. | The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | Polymorphisms in genes related to oxidative stress (MPO, MnSOD, /"CAT"/) and survival after treatment for breast cancer. | The proximate cause of /"cancer"/ cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, /"CAT"/, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both /"CAT"/ TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a 3-fold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. /"X-ray repair cross-complementing gene 1"/ (/"XRCC1"/; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for /"IFN-gamma"/ (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: /"IFN-gamma"/ (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that /"IFN-gamma"/ (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for /"IFN-gamma"/, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and /"excision repair cross-complementing gene 1"/ (/"ERCC1"/; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The /"ERCC1"/ polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and /"ERCC1"/ stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), /"xeroderma pigmentosum complementary group D"/ (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and /"IL-10"/ (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the /"IL-10"/ polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, /"IL-10"/, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and /"IFN-alpha"/ either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and /"IFN-alpha"/ either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with /"interleukin (IL)-2"/ and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with /"interleukin (IL)-2"/ and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15709194 | Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | Impact of gene polymorphisms on clinical outcome for stage IV /"melanoma"/ patients treated with biochemotherapy: an exploratory study. | PURPOSE: Biochemotherapy can achieve high response rates in advanced /"melanoma"/, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV /"melanoma"/ patients treated with biochemotherapy. EXPERIMENTAL DESIGN: Ninety patients with stage IV /"melanoma"/ were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with /"interleukin (IL)-2"/ and IFN-alpha either with or without tamoxifen. Cytokine gene polymorphisms for IFN-gamma (+874A-->T) and IL-10 (-1082G-->A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined. RESULTS: IFN-gamma (+874A-->T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-gamma (+874A-->T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-gamma, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more "favorable" polymorphisms had a better outcome. CONCLUSIONS: Cytokine gene polymorphisms predicted clinical outcome for advanced /"melanoma"/ patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings. | [
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15718509 | Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage. | BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha1-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. METHODS: A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH. | /"Alpha1-antichymotrypsin"/ gene (/"SERPINA3"/) A/T polymorphism as a risk factor for /"aneurysmal subarachnoid hemorrhage"/. | BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (/"SERPINA3"/), known previously as the /"alpha1-antichymotrypsin"/, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the /"SERPINA3"/ gene influences expression of /"SERPINA3"/ protein. /"SERPINA3"/ can be related to /"aneurysmal subarachnoid hemorrhage"/ (/"SAH"/) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of /"SERPINA3"/ A/T polymorphism in patients with aneurysmal /"SAH"/ compared with healthy controls. METHODS: A total of 180 patients with aneurysmal /"SAH"/ and 263 healthy controls were genotyped for the /"SERPINA3"/ A/T polymorphism. Aneurysmal /"SAH"/ was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. /"SERPINA3"/ polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The /"SERPINA3"/ genotype distribution in patients with aneurysmal /"SAH"/ (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the /"SERPINA3"/ influences the risk for aneurysmal /"SAH"/ independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of /"SERPINA3"/ gene is associated with the risk factor for aneurysmal /"SAH"/. | [
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15718509 | Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage. | BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha1-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. METHODS: A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH. | /"Alpha1-antichymotrypsin"/ gene (/"SERPINA3"/) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage. | BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (/"SERPINA3"/), known previously as the /"alpha1-antichymotrypsin"/, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the /"SERPINA3"/ gene influences expression of /"SERPINA3"/ protein. /"SERPINA3"/ can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of /"SERPINA3"/ A/T polymorphism in patients with /"aneurysmal"/ SAH compared with healthy controls. METHODS: A total of 180 patients with /"aneurysmal"/ SAH and 263 healthy controls were genotyped for the /"SERPINA3"/ A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. /"SERPINA3"/ polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The /"SERPINA3"/ genotype distribution in patients with /"aneurysmal"/ SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the /"SERPINA3"/ influences the risk for /"aneurysmal"/ SAH independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of /"SERPINA3"/ gene is associated with the risk factor for /"aneurysmal"/ SAH. | [
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15734955 | Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. | The variability in DNA repair capacity of the general population may depend in part upon common variants in DNA repair genes. X-ray repair cross complementing group 1 (XRCC1) is an important DNA base excision repair gene and exhibits polymorphic variation. Using the Long Island Breast Cancer Study Project, a population-based case-control study, we evaluated the hypothesis that two common single nucleotide polymorphisms of XRCC1 (codon 194 Arg-->Trp and 399 Arg-->Gln) influence breast cancer susceptibility and interact with polycyclic aromatic hydrocarbon (PAH)-DNA adducts, cigarette smoking, and intake of fruits and vegetables and antioxidants. The available sample for genotyping included 1,067 cases and 1,110 controls. Genotyping was done by a high-throughput single-nucleotide extension assay with fluorescence polarization detection of the incorporated nucleotide. We observed no significant increases in risk among all subjects who were carriers of XRCC1 194Trp or 399Gln alleles. Among never smokers, we observed an increased risk of breast cancer in 399Gln carriers [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7). Further analysis indicated a suggestive weak additive interaction between the 399Gln allele and detectable PAH-DNA adducts (OR for exposure with mutant genotype, 1.9; 95% CI, 1.2-3.1). The estimated age-adjusted interaction contrast ratio (ICR) and 95% CI (ICR, 0.38; 95% CI, -0.32 to 1.10) indicated that the departure from additivity was not statistically significant, but that there was some suggestion of a relative excess risk due to the interaction. In subjects with at least one copy of XRCC1 194Trp allele, there was a moderate interaction with high intake of fruits and vegetables (>/=35 half-cup servings per week of any fruits, fruit juices, and vegetables, OR, 0.58; 95% CI, 0.38-0.89; ICR, -0.49; 95% CI, -0.03 to -0.95), and dietary plus supplement antioxidant intake with 33% to 42% decreases in breast cancer risk compared with those with the Arg194Arg genotype and low-intake individuals. These results do not show that the two genetic polymorphisms of XRCC1 independently influence breast cancer risk. However, there is evidence for interactions between the two XRCC1 single nucleotide polymorphisms and PAH-DNA adducts or fruit and vegetable and antioxidant intake on breast cancer risk. Further understanding of the biological function of XRCC1 variants and their interactions with PAH-DNA adducts, antioxidants, and other genes in the pathway are needed. | Polymorphisms in /"XRCC1"/ modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and /"breast cancer"/ risk. | The variability in DNA repair capacity of the general population may depend in part upon common variants in DNA repair genes. /"X-ray repair cross complementing group 1"/ (/"XRCC1"/) is an important DNA base excision repair gene and exhibits polymorphic variation. Using the Long Island Breast Cancer Study Project, a population-based case-control study, we evaluated the hypothesis that two common single nucleotide polymorphisms of /"XRCC1"/ (codon 194 Arg-->Trp and 399 Arg-->Gln) influence /"breast cancer"/ susceptibility and interact with polycyclic aromatic hydrocarbon (PAH)-DNA adducts, cigarette smoking, and intake of fruits and vegetables and antioxidants. The available sample for genotyping included 1,067 cases and 1,110 controls. Genotyping was done by a high-throughput single-nucleotide extension assay with fluorescence polarization detection of the incorporated nucleotide. We observed no significant increases in risk among all subjects who were carriers of /"XRCC1"/ 194Trp or 399Gln alleles. Among never smokers, we observed an increased risk of /"breast cancer"/ in 399Gln carriers [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7). Further analysis indicated a suggestive weak additive interaction between the 399Gln allele and detectable PAH-DNA adducts (OR for exposure with mutant genotype, 1.9; 95% CI, 1.2-3.1). The estimated age-adjusted interaction contrast ratio (ICR) and 95% CI (ICR, 0.38; 95% CI, -0.32 to 1.10) indicated that the departure from additivity was not statistically significant, but that there was some suggestion of a relative excess risk due to the interaction. In subjects with at least one copy of /"XRCC1"/ 194Trp allele, there was a moderate interaction with high intake of fruits and vegetables (>/=35 half-cup servings per week of any fruits, fruit juices, and vegetables, OR, 0.58; 95% CI, 0.38-0.89; ICR, -0.49; 95% CI, -0.03 to -0.95), and dietary plus supplement antioxidant intake with 33% to 42% decreases in /"breast cancer"/ risk compared with those with the Arg194Arg genotype and low-intake individuals. These results do not show that the two genetic polymorphisms of /"XRCC1"/ independently influence /"breast cancer"/ risk. However, there is evidence for interactions between the two /"XRCC1"/ single nucleotide polymorphisms and PAH-DNA adducts or fruit and vegetable and antioxidant intake on /"breast cancer"/ risk. Further understanding of the biological function of /"XRCC1"/ variants and their interactions with PAH-DNA adducts, antioxidants, and other genes in the pathway are needed. | [
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15738346 | PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites. | PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women. | /"PGC-1alpha"/ Gly482Ser polymorphism associates with /"hypertension"/ among Danish whites. | /"PGC-1alpha"/ is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of /"PGC-1alpha"/ has previously shown association with arterial /"hypertension"/ among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial /"hypertension"/ were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of /"hypertension"/ and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for /"hypertension"/ compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of /"PGC-1alpha"/ Gly482Ser confers a significantly reduced risk of /"hypertension"/ in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women. | [
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15772682 | Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. | Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P=0.04). Particular IL-10 genotypes were associated with SSc-related autoantibodies. These results suggest that IL-10 genotypes contribute to the etiology of scleroderma. | /"Interleukin-10"/ genotypes are associated with /"systemic sclerosis"/ and influence disease-associated autoimmune responses. | /"Systemic sclerosis"/ (/"SSc"/; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. /"Interleukin-10"/ (/"IL-10"/) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain /"IL-10"/ genotypes are risk factors for the development of /"SSc"/ and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese /"SSc"/ patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for /"SSc"/-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse /"SSc"/ as compared to controls (P=0.04). Particular /"IL-10"/ genotypes were associated with /"SSc"/-related autoantibodies. These results suggest that /"IL-10"/ genotypes contribute to the etiology of scleroderma. | [
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15772682 | Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. | Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P=0.04). Particular IL-10 genotypes were associated with SSc-related autoantibodies. These results suggest that IL-10 genotypes contribute to the etiology of scleroderma. | /"Interleukin-10"/ genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. | Systemic sclerosis (SSc; /"scleroderma"/) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. /"Interleukin-10"/ (/"IL-10"/) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain /"IL-10"/ genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P=0.04). Particular /"IL-10"/ genotypes were associated with SSc-related autoantibodies. These results suggest that /"IL-10"/ genotypes contribute to the etiology of /"scleroderma"/. | [
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15776395 | Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. | As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large T1D sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5x10(-8)) for a T1D locus in the CD25 region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-10)). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region. | Localization of a /"type 1 diabetes"/ locus in the /"IL2RA"///"CD25"/ region by use of tag single-nucleotide polymorphisms. | As part of an ongoing search for genes associated with /"type 1 diabetes"/ (/"T1D"/), a common autoimmune disease, we tested the biological candidate gene /"IL2RA"/ (/"CD25"/), which encodes a subunit (/"IL-2R alpha"/) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large /"T1D"/ sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5x10(-8)) for a /"T1D"/ locus in the /"CD25"/ region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-10)). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region. | [
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"entity_id": "D003922",
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"text_name": "type 1 diabetes"
} | Yes |
15776395 | Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. | As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large T1D sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5x10(-8)) for a T1D locus in the CD25 region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-10)). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region. | Localization of a type 1 diabetes locus in the /"IL2RA"///"CD25"/ region by use of tag single-nucleotide polymorphisms. | As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common /"autoimmune disease"/, we tested the biological candidate gene /"IL2RA"/ (/"CD25"/), which encodes a subunit (/"IL-2R alpha"/) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large T1D sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5x10(-8)) for a T1D locus in the /"CD25"/ region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-10)). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region. | [
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15776585 | [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. | We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and NIDDM subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major NIDDM predisposing locus for the negroid population of Senegal. | [Genetic polymorphism of /"pyruvate dehydrogenase kinase 4"/ (/"PDK4"/), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the /"NIDDM"/ population of Senegal]. | We reported a study about three candidate genes which may be involved in /"non-insulin dependent diabetes mellitus"/ (/"NIDDM"/): /"Pyruvate Dehydrogenase Kinase 4"/ (/"PDK4"/), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and /"NIDDM"/ subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for /"PDK4"/ polymorphism. These results suggest that none of these gene variants is a major /"NIDDM"/ predisposing locus for the negroid population of Senegal. | [
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15776585 | [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. | We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and NIDDM subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major NIDDM predisposing locus for the negroid population of Senegal. | [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and /"fatty acid binding protein 2"/ (/"FABP2"/) in the /"NIDDM"/ population of Senegal]. | We reported a study about three candidate genes which may be involved in /"non-insulin dependent diabetes mellitus"/ (/"NIDDM"/): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and /"Fatty Acid Binding Protein 2"/ (/"FABP2"/). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and /"NIDDM"/ subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major /"NIDDM"/ predisposing locus for the negroid population of Senegal. | [
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} | Yes |
15776585 | [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. | We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and NIDDM subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major NIDDM predisposing locus for the negroid population of Senegal. | [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), /"paraoxonase 2"/ (/"PON2"/), and fatty acid binding protein 2 (FABP2) in the /"NIDDM"/ population of Senegal]. | We reported a study about three candidate genes which may be involved in /"non-insulin dependent diabetes mellitus"/ (/"NIDDM"/): Pyruvate Dehydrogenase Kinase 4 (PDK4), /"Paraoxonase 2"/ (/"PON2"/) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (S n gal) by PCR-RFLP techniques. There was no significant difference between both control and /"NIDDM"/ subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major /"NIDDM"/ predisposing locus for the negroid population of Senegal. | [
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15781196 | Four new mutations in the BCHE gene of human butyrylcholinesterase in a Brazilian blood donor sample. | The genetic variation of human butyrylcholinesterase has been associated with height, body mass index, Alzheimer's disease, and response to xenobiotic agents. The present study reports four new mutations, found in the exon 2 of the BCHE gene, in a sample from 3001 Brazilian blood donors. The three nonsynonymous mutations and one synonymous mutation detected are: 223G-->C, G75R; 270A-->C, E90 D; 297T-->G, I99 M; 486T-->C, A162 A, respectively. All these variants are rare: 0.093+/-0.093% for the missense mutations and 0.137+/-0.137% for the synonymous mutation. A table with the 58 non-usual variants of butyrylcholinesterase is also presented. | Four new mutations in the /"BCHE"/ gene of human /"butyrylcholinesterase"/ in a Brazilian blood donor sample. | The genetic variation of human /"butyrylcholinesterase"/ has been associated with height, body mass index, /"Alzheimer's disease"/, and response to xenobiotic agents. The present study reports four new mutations, found in the exon 2 of the /"BCHE"/ gene, in a sample from 3001 Brazilian blood donors. The three nonsynonymous mutations and one synonymous mutation detected are: 223G-->C, G75R; 270A-->C, E90 D; 297T-->G, I99 M; 486T-->C, A162 A, respectively. All these variants are rare: 0.093+/-0.093% for the missense mutations and 0.137+/-0.137% for the synonymous mutation. A table with the 58 non-usual variants of /"butyrylcholinesterase"/ is also presented. | [
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15788153 | Testosterone responsiveness of spleen and liver in female lymphotoxin beta receptor-deficient mice resistant to blood-stage malaria. | Disrupted signaling through lymphotoxin beta receptor (LTbetaR) results in severe defects of the spleen and even loss of all other secondary lymphoid tissues, making mice susceptible to diverse infectious agents. Surprisingly, however, we find that female LTbetaR-deficient mice are even more resistant to blood stages of Plasmodium chabaudi malaria than wild-type C57BL/6 mice. Higher resistance of LTbetaR-deficient mice correlates with an earlier onset of reticulocytosis, and the period of anemia is shorter. After surviving fulminant parasitemias of about 35%, mice develop long-lasting protective immunity against homologous rechallenge, with both spleen and liver acting as anti-malaria effectors. Testosterone suppresses resistance, i.e. all mice succumb to infections during or shortly after peak parasitemia. At peak parasitemia, testosterone does not essentially affect cellularity and apoptosis in the spleen, but aggravates liver pathology in terms of increased cell swelling, numbers of apoptotic and binucleated cells and reduced serum alkaline phosphatase levels, and conversely, reduces inflammatory lymphocytic infiltrates in the liver. In the spleen, hybridization of cDNA arrays identified only a few testosterone-induced changes in gene expression, in particular upregulation of INFgamma and IFN-regulated genes. By contrast, a much larger number of testosterone-affectable genes was observed in the liver, including genes involved in regulation of the extracellular matrix, in chemokine and cytokine signaling, and in cell cycle control. Collectively, our data suggest that testosterone dysregulates the inflammatory response in spleen and liver during their differentiation to anti-malaria effectors in malaria-resistant female LTbetaR-deficient mice, thus contributing to the testosterone-induced lethal outcome of malaria. | Testosterone responsiveness of spleen and liver in female /"lymphotoxin beta receptor"/-deficient mice resistant to blood-stage /"malaria"/. | Disrupted signaling through /"lymphotoxin beta receptor"/ (/"LTbetaR"/) results in severe defects of the spleen and even loss of all other secondary lymphoid tissues, making mice susceptible to diverse infectious agents. Surprisingly, however, we find that female /"LTbetaR"/-deficient mice are even more resistant to blood stages of Plasmodium chabaudi /"malaria"/ than wild-type C57BL/6 mice. Higher resistance of /"LTbetaR"/-deficient mice correlates with an earlier onset of reticulocytosis, and the period of anemia is shorter. After surviving fulminant parasitemias of about 35%, mice develop long-lasting protective immunity against homologous rechallenge, with both spleen and liver acting as anti-/"malaria"/ effectors. Testosterone suppresses resistance, i.e. all mice succumb to infections during or shortly after peak parasitemia. At peak parasitemia, testosterone does not essentially affect cellularity and apoptosis in the spleen, but aggravates liver pathology in terms of increased cell swelling, numbers of apoptotic and binucleated cells and reduced serum alkaline phosphatase levels, and conversely, reduces inflammatory lymphocytic infiltrates in the liver. In the spleen, hybridization of cDNA arrays identified only a few testosterone-induced changes in gene expression, in particular upregulation of INFgamma and IFN-regulated genes. By contrast, a much larger number of testosterone-affectable genes was observed in the liver, including genes involved in regulation of the extracellular matrix, in chemokine and cytokine signaling, and in cell cycle control. Collectively, our data suggest that testosterone dysregulates the inflammatory response in spleen and liver during their differentiation to anti-/"malaria"/ effectors in /"malaria"/-resistant female /"LTbetaR"/-deficient mice, thus contributing to the testosterone-induced lethal outcome of /"malaria"/. | [
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15788153 | Testosterone responsiveness of spleen and liver in female lymphotoxin beta receptor-deficient mice resistant to blood-stage malaria. | Disrupted signaling through lymphotoxin beta receptor (LTbetaR) results in severe defects of the spleen and even loss of all other secondary lymphoid tissues, making mice susceptible to diverse infectious agents. Surprisingly, however, we find that female LTbetaR-deficient mice are even more resistant to blood stages of Plasmodium chabaudi malaria than wild-type C57BL/6 mice. Higher resistance of LTbetaR-deficient mice correlates with an earlier onset of reticulocytosis, and the period of anemia is shorter. After surviving fulminant parasitemias of about 35%, mice develop long-lasting protective immunity against homologous rechallenge, with both spleen and liver acting as anti-malaria effectors. Testosterone suppresses resistance, i.e. all mice succumb to infections during or shortly after peak parasitemia. At peak parasitemia, testosterone does not essentially affect cellularity and apoptosis in the spleen, but aggravates liver pathology in terms of increased cell swelling, numbers of apoptotic and binucleated cells and reduced serum alkaline phosphatase levels, and conversely, reduces inflammatory lymphocytic infiltrates in the liver. In the spleen, hybridization of cDNA arrays identified only a few testosterone-induced changes in gene expression, in particular upregulation of INFgamma and IFN-regulated genes. By contrast, a much larger number of testosterone-affectable genes was observed in the liver, including genes involved in regulation of the extracellular matrix, in chemokine and cytokine signaling, and in cell cycle control. Collectively, our data suggest that testosterone dysregulates the inflammatory response in spleen and liver during their differentiation to anti-malaria effectors in malaria-resistant female LTbetaR-deficient mice, thus contributing to the testosterone-induced lethal outcome of malaria. | Testosterone responsiveness of spleen and liver in female /"lymphotoxin beta receptor"/-deficient mice resistant to blood-stage malaria. | Disrupted signaling through /"lymphotoxin beta receptor"/ (/"LTbetaR"/) results in severe defects of the spleen and even loss of all other secondary lymphoid tissues, making mice susceptible to diverse infectious agents. Surprisingly, however, we find that female /"LTbetaR"/-deficient mice are even more resistant to blood stages of Plasmodium chabaudi malaria than wild-type C57BL/6 mice. Higher resistance of /"LTbetaR"/-deficient mice correlates with an earlier onset of reticulocytosis, and the period of anemia is shorter. After surviving fulminant /"parasitemias"/ of about 35%, mice develop long-lasting protective immunity against homologous rechallenge, with both spleen and liver acting as anti-malaria effectors. Testosterone suppresses resistance, i.e. all mice succumb to infections during or shortly after peak /"parasitemia"/. At peak /"parasitemia"/, testosterone does not essentially affect cellularity and apoptosis in the spleen, but aggravates liver pathology in terms of increased cell swelling, numbers of apoptotic and binucleated cells and reduced serum alkaline phosphatase levels, and conversely, reduces inflammatory lymphocytic infiltrates in the liver. In the spleen, hybridization of cDNA arrays identified only a few testosterone-induced changes in gene expression, in particular upregulation of INFgamma and IFN-regulated genes. By contrast, a much larger number of testosterone-affectable genes was observed in the liver, including genes involved in regulation of the extracellular matrix, in chemokine and cytokine signaling, and in cell cycle control. Collectively, our data suggest that testosterone dysregulates the inflammatory response in spleen and liver during their differentiation to anti-malaria effectors in malaria-resistant female /"LTbetaR"/-deficient mice, thus contributing to the testosterone-induced lethal outcome of malaria. | [
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15809232 | Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers. | AIMS: To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. METHODS: Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. RESULTS: Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. CONCLUSIONS: APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events. | Polymorphisms of /"apolipoprotein E"/ and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers. | AIMS: To investigate the influence of /"apolipoprotein E"/ (/"APOE"/) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery /"atherosclerosis"/ in alcoholism. METHODS: Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. RESULTS: Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the /"APO E"/ epsilon4 allele were more liable to develop /"atherosclerotic"/ changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. CONCLUSIONS: /"APO E"/ polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the /"APO E"/ epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized /"atherosclerosis"/ the consequences could involve both cardiac and cerebrovascular events. | [
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15809232 | Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers. | AIMS: To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. METHODS: Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. RESULTS: Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. CONCLUSIONS: APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events. | Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and /"carotid atherosclerosis"/ in heavy drinkers. | AIMS: To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (/"ACE"/) gene polymorphisms on carotid artery atherosclerosis in alcoholism. METHODS: Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. RESULTS: Multivariate regression analysis showed that of all the known risk factors the greatest impact on /"carotid atherosclerosis"/ in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between /"ACE"/ I/D polymorphism and /"carotid atherosclerosis"/. CONCLUSIONS: APO E polymorphism can increase the risk of /"carotid atherosclerosis"/ development in an alcoholic subject. The association of the APO E epsilon4 allele with /"carotid atherosclerosis"/ was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events. | [
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15824150 | Genetic polymorphisms of ataxia telangiectasia mutated and breast cancer risk. | To evaluate the role of genetic polymorphisms of ataxia telangiectasia mutated (ATM) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the ATM polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five ATM alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The ATM IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women. | Genetic polymorphisms of /"ataxia telangiectasia mutated"/ and /"breast cancer"/ risk. | To evaluate the role of genetic polymorphisms of /"ataxia telangiectasia mutated"/ (/"ATM"/) in the etiology of /"breast cancer"/, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident /"breast cancer"/ cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the /"ATM"/ polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five /"ATM"/ alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The /"ATM"/ IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with /"increased breast cancer"/ risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of /"breast cancer"/ with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with /"increased breast cancer"/ risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of /"breast cancer"/, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of /"breast cancer"/ increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of /"ATM"/ play an important role in the development of /"breast cancer"/ in Korean women. | [
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15824150 | Genetic polymorphisms of ataxia telangiectasia mutated and breast cancer risk. | To evaluate the role of genetic polymorphisms of ataxia telangiectasia mutated (ATM) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the ATM polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five ATM alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The ATM IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women. | Genetic polymorphisms of /"ataxia telangiectasia mutated"/ and breast cancer risk. | To evaluate the role of genetic polymorphisms of /"ataxia telangiectasia mutated"/ (/"ATM"/) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 /"cancer"/-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the /"ATM"/ polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five /"ATM"/ alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The /"ATM"/ IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of /"ATM"/ play an important role in the development of breast cancer in Korean women. | [
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"text_name": "cancer"
} | No |
15824176 | The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. | The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G>A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including androgenetic alopecia, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P < 0.0001). This inverse association between the A allele and baldness was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of alopecia. | The E211 G>A /"androgen receptor"/ polymorphism is associated with a decreased risk of /"metastatic prostate cancer"/ and androgenetic alopecia. | The /"androgen receptor"/ (/"AR"/) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. /"Prostate cancer"/ is androgen dependent, implicating /"AR"/ in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with /"prostate cancer"/, suggesting shared androgen pathways. The CAG and GGC repeats in the /"AR"/ have been studied extensively as markers of /"prostate cancer"/ susceptibility, with inconclusive findings, whereas the /"AR"/-E211 G>A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in /"prostate cancer"/, including androgenetic alopecia, in an Australian population-based case-control study. In 815 /"prostate cancer"/ cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of /"prostate cancer"/, however, the proportion of A-allele carriers in /"metastatic prostate cancer"/ (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P < 0.0001). This inverse association between the A allele and baldness was independent of /"prostate cancer"/ status (P for interaction = 0.2). These results suggest that the /"AR"/-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of /"metastatic prostate cancer"/ and a lower risk of alopecia. | [
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15824176 | The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. | The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G>A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including androgenetic alopecia, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P < 0.0001). This inverse association between the A allele and baldness was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of alopecia. | The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and /"androgenetic alopecia"/. | The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, /"androgenetic alopecia"/, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and /"GGC"/ repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G>A polymorphism has been associated with /"androgenetic alopecia"/. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including /"androgenetic alopecia"/, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex /"alopecia"/ alone (13%, P = 0.001) or in combination with frontal /"alopecia"/ (7%, P < 0.0001). This inverse association between the A allele and /"baldness"/ was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of /"alopecia"/. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote /"steatosis"/ and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related /"steatosis"/ are unknown. Hyperhomocysteinemia causes /"steatosis"/, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and /"steatosis"/ grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). /"Steatosis"/ correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. /"Steatosis"/ above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of /"steatosis"/ were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of /"steatosis"/ was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, /"steatosis"/ was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, /"steatosis"/, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and /"steatosis"/ (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of /"steatosis"/, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and fibrosis in /"chronic hepatitis C"/ patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of /"chronic hepatitis C"/ (/"CHC"/). One hundred sixteen /"CHC"/ patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in /"CHC"/. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | /"Hyperhomocysteinemia"/ and the /"MTHFR"/ C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. /"Hyperhomocysteinemia"/ causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces /"hyperhomocysteinemia"/. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. /"Hyperhomocysteinemia"/ was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with /"hyperhomocysteinemia"/ (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for /"hyperhomocysteinemia"/ plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), /"liver fibrosis"/ (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, /"liver fibrosis"/ was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of /"liver fibrosis"/ in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of /"hepatitis C virus"/ (/"HCV"/)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of /"HCV-related steatosis"/ and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, /"HCV"/ genotypes, /"HCV"/ RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and /"HCV"/ genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and /"fibrosis"/ in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, /"fibrosis"/ and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and /"fibrosis"/. Steatosis above 20% was significantly associated with /"fibrosis"/. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, /"fibrosis"/ was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and /"fibrosis"/ in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, /"fibrosis"/ and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and /"fibrosis"/. Steatosis above 20% was significantly associated with /"fibrosis"/. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, /"fibrosis"/ was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15834927 | Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | Hyperhomocysteinemia and the /"MTHFR"/ C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. | The factors and mechanisms implicated in the development of /"hepatitis C virus"/ (/"HCV"/)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of /"HCV-related steatosis"/ and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, /"HCV"/ genotypes, /"HCV"/ RNA levels, homocysteinemia, and the /"MTHFR"/ C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of /"MTHFR"/ (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the /"MTHFR"/ gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the /"MTHFR"/ polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and /"HCV"/ genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, /"MTHFR"/, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the /"MTHFR"/ C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. | [
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15837080 | Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, MI or premature MI in our population. | Association study of the /"thrombomodulin"/ -33G>A polymorphism with /"coronary artery disease"/ and myocardial infarction in Chinese Han population. | BACKGROUND: /"Thrombomodulin"/ (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to /"coronary artery disease"/ (/"CAD"/) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified /"CAD"/ or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between /"CAD"/ patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with /"CAD"/, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with /"CAD"/, MI or premature MI in our population. | [
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"text_name": "coronary artery disease"
} | Yes |
15837080 | Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, MI or premature MI in our population. | Association study of the /"thrombomodulin"/ -33G>A polymorphism with coronary artery disease and /"myocardial infarction"/ in Chinese Han population. | BACKGROUND: /"Thrombomodulin"/ (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or /"myocardial infarction"/ (/"MI"/) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute /"MI"/ and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between /"MI"/ patients (11.5%) and controls (P=0.163), or between premature /"MI"/ patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with /"MI"/, and 77.7%:22.3% in patients with premature /"MI"/, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, /"MI"/ or premature /"MI"/ in our population. | [
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"entity_id": "7056",
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] | {
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"entity_id": "7056",
"entity_type": "Gene",
"text_name": "thrombomodulin"
} | {
"begin_idx": "93",
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"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
} | Yes |
15837080 | Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, MI or premature MI in our population. | Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and /"myocardial infarction"/ in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the /"thrombin"/-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or /"myocardial infarction"/ (/"MI"/) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute /"MI"/ and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between /"MI"/ patients (11.5%) and controls (P=0.163), or between premature /"MI"/ patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with /"MI"/, and 77.7%:22.3% in patients with premature /"MI"/, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, /"MI"/ or premature /"MI"/ in our population. | [
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"begin_idx": "251",
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"entity_id": "2147",
"entity_type": "Gene",
"text_name": "thrombin"
} | {
"begin_idx": "93",
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"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
} | No |
15837080 | Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the thrombin-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to coronary artery disease (CAD) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified CAD or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between CAD patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with CAD, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with CAD, MI or premature MI in our population. | Association study of the thrombomodulin -33G>A polymorphism with /"coronary artery disease"/ and myocardial infarction in Chinese Han population. | BACKGROUND: Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein cofactor in the /"thrombin"/-mediated activation of protein C. Recently, conflicting data have been reported regarding the possible contribution of the TM -33G>A polymorphism to /"coronary artery disease"/ (/"CAD"/) or myocardial infarction (MI) in some Asian populations. We investigated this polymorphism in northern Han Chinese. METHODS: We performed a case-control study, including 808 patients with angiographically verified /"CAD"/ or a history of an acute MI and 813 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We did not find a significant difference in the frequency of the A allele between /"CAD"/ patients (11%) and controls (9.8%; P=0.249), between MI patients (11.5%) and controls (P=0.163), or between premature MI patients (11.7%) and controls (P=0.265). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG: (GA/AA) was 81.4%:18.6% in controls, 79.7%:20.3% in patients with /"CAD"/, 78.8%:21.2% in patients with MI, and 77.7%:22.3% in patients with premature MI, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. CONCLUSIONS: Our results seemed not to support a significant association of the TM -33G>A polymorphism with /"CAD"/, MI or premature MI in our population. | [
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"text_name": "thrombin"
},
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"entity_id": "7056",
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"text_name": "thrombomodulin"
},
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}
] | {
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} | {
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} | No |
15876692 | CAG repeat polymorphism in the androgen receptor (AR) gene of SBMA patients and a control group. | Spinobulbar muscular atrophy (SBMA) is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria and mild androgen insensitivity. SBMA is caused by CAG repeat expansion in the androgen receptor gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of SBMA (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of SBMA was molecularly confirmed. The ranges are similar to those reported for other populations. | CAG repeat polymorphism in the /"androgen receptor"/ (/"AR"/) gene of /"SBMA"/MA"/ patients and a control group. | /"Spinobulbar muscular atrophy"/ (/"SBMA"/MA"/) is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria and mild androgen insensitivity. /"SBMA"/MA"/ is caused by CAG repeat expansion in the /"androgen receptor"/ gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of /"SBMA"/MA"/ (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of /"SBMA"/MA"/ was molecularly confirmed. The ranges are similar to those reported for other populations. | [
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"entity_id": "D003680",
"entity_type": "Disease",
"text_name": "dysphagia"
},
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"entity_id": "D004401",
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"text_name": "SBMA"
},
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"entity_type": "Gene",
"text_name": "SBMA"
}
] | {
"begin_idx": "31",
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"text_name": "androgen receptor"
} | {
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"entity_id": "D020966",
"entity_type": "Disease",
"text_name": "Spinobulbar muscular atrophy"
} | Yes |
15876692 | CAG repeat polymorphism in the androgen receptor (AR) gene of SBMA patients and a control group. | Spinobulbar muscular atrophy (SBMA) is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria and mild androgen insensitivity. SBMA is caused by CAG repeat expansion in the androgen receptor gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of SBMA (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of SBMA was molecularly confirmed. The ranges are similar to those reported for other populations. | CAG repeat polymorphism in the /"androgen receptor"/ (/"AR"/) gene of /"SBMA"/ patients and a control group. | Spinobulbar muscular atrophy (/"SBMA"/) is an X-linked form of motor neuron disease characterized by progressive /"atrophy of the muscles"/, dysphagia, dysarthria and mild androgen insensitivity. /"SBMA"/ is caused by CAG repeat expansion in the /"androgen receptor"/ gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of /"SBMA"/ (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of /"SBMA"/ was molecularly confirmed. The ranges are similar to those reported for other populations. | [
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15886521 | Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | Obesity and genetic polymorphism of ERCC2 and /"ERCC4"/ as modifiers of risk of /"breast cancer"/. | To evaluate the relationship of genetic polymorphisms of ERCC2 and /"ERCC4"/ genes, both involved in nucleotide excision repair (NER), and the risk of /"breast cancer"/, a hospital-based case-control study was conducted in Korea. Histologically confirmed /"breast cancer"/ cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and /"ERCC4"/ Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of /"breast cancer"/, women with both ERCC2 A allele- and /"ERCC4"/ C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of /"breast cancer"/ compared to women concurrently carrying the ERCC2 GG and /"ERCC4"/ TT genotypes. The /"breast cancer"/ risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between /"ERCC4"/ genotype and body mass idnex (BMI) for the /"breast cancer"/ risk; the /"ERCC4"/ C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) /"breast cancer"/ risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and /"ERCC4"/ Ser(835)Ser genotypes might be associated with /"breast cancer"/ risk in Korean women. | [
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} | Yes |
15886521 | Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | Obesity and genetic polymorphism of /"ERCC2"/ and ERCC4 as modifiers of risk of /"breast cancer"/. | To evaluate the relationship of genetic polymorphisms of /"ERCC2"/ and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of /"breast cancer"/, a hospital-based case-control study was conducted in Korea. Histologically confirmed /"breast cancer"/ cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. /"ERCC2"/ Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of /"breast cancer"/, women with both /"ERCC2"/ A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of /"breast cancer"/ compared to women concurrently carrying the /"ERCC2"/ GG and ERCC4 TT genotypes. The /"breast cancer"/ risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the /"breast cancer"/ risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) /"breast cancer"/ risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of /"ERCC2"/ Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with /"breast cancer"/ risk in Korean women. | [
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15886521 | Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | /"Obesity"/ and genetic polymorphism of ERCC2 and /"ERCC4"/ as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of ERCC2 and /"ERCC4"/ genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and /"ERCC4"/ Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and /"ERCC4"/ C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and /"ERCC4"/ TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between /"ERCC4"/ genotype and body mass idnex (BMI) for the breast cancer risk; the /"ERCC4"/ C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in /"obese"/ women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and /"ERCC4"/ Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | [
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15886521 | Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | Obesity and genetic polymorphism of /"ERCC2"/ and ERCC4 as modifiers of risk of breast cancer. | To evaluate the relationship of genetic polymorphisms of /"ERCC2"/ and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of /"cancer"/ were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. /"ERCC2"/ Asp(312)Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser(835)Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both /"ERCC2"/ A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the /"ERCC2"/ GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m(2)) with a borderline significance. Our finding suggests that the combined effect of /"ERCC2"/ Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women. | [
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15886814 | Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome. A possible implication of fractalkine in inflammatory activation. | Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD.720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not "balanced" by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk. | Opposite effects of /"CX3CR1"/ receptor polymorphisms V249I and T280M on the development of /"acute coronary syndrome"/. A possible implication of fractalkine in inflammatory activation. | Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor /"CX3CR1"/ contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the /"CX3CR1"/T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another /"CX3CR1"/ polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of /"CX3CR1"/ with coronary artery disease (CAD) and with /"acute coronary syndrome"/ (/"ACS"/). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD.720 (62.5%) individuals showed significant CAD with an /"ACS"/ prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of /"ACS"/ in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of /"ACS"/ (OR=1.6, P<0.04). During /"ACS"/ these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of /"ACS"/. The presence of I249 not "balanced" by M280 confers an elevated risk of /"ACS"/. A FKN-mediated enhanced inflammatory activation might explain this increased risk. | [
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15886814 | Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome. A possible implication of fractalkine in inflammatory activation. | Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD.720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not "balanced" by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk. | Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome. A possible implication of /"fractalkine"/ in inflammatory activation. | Several lines of evidence suggest that the chemokine /"fractalkine"/ (/"FKN"/) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with /"coronary artery disease"/ (/"CAD"/) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand /"FKN"/ and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected /"CAD"/.720 (62.5%) individuals showed significant /"CAD"/ with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with /"CAD"/. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of /"FKN"/ and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of /"CAD"/. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not "balanced" by M280 confers an elevated risk of ACS. A /"FKN"/-mediated enhanced inflammatory activation might explain this increased risk. | [
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15893594 | Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | Genetic variants of angiotensin converting enzyme and /"methylenetetrahydrofolate reductase"/ may act in combination to increase /"migraine"/ susceptibility. | /"Migraine"/, with and without aura (/"MA"/ and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in /"migraine"/ risk and whether this variant might act in combination with the previously implicated /"MTHFR"/ C677T genetic variant in 270 /"migraine"/ cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the /"migraine"/ group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the /"MTHFR"/ C677T, provided evidence that the /"MTHFR"/ (TT) and ACE (ID/DD) genotypes act in combination to increase /"migraine"/ susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the /"MA"/ subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to /"migraine"/ susceptibility and also appears to act in combination with the C677T variant in the /"MTHFR"/ gene to confer a stronger influence on the disease. | [
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15893594 | Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | Genetic variants of /"angiotensin converting enzyme"/ and methylenetetrahydrofolate reductase may act in combination to increase /"migraine"/ susceptibility. | /"Migraine"/, with and without aura (/"MA"/ and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in /"migraine"/ risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 /"migraine"/ cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the /"migraine"/ group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase /"migraine"/ susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the /"MA"/ subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to /"migraine"/ susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | [
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15893594 | Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | Genetic variants of angiotensin converting enzyme and /"methylenetetrahydrofolate reductase"/ may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and /"complex neurovascular disorder"/ that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated /"MTHFR"/ C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the /"MTHFR"/ C677T, provided evidence that the /"MTHFR"/ (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the /"MTHFR"/ gene to confer a stronger influence on the disease. | [
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15893594 | Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | Genetic variants of /"angiotensin converting enzyme"/ and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. | Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the /"DD"//ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID//"DD"/) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease. | [
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15901993 | Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma. | Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA. | Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to /"cholangiocarcinoma"/. | Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and /"NAT2"/ polymorphisms and /"cholangiocarcinoma"/ (/"CCA"/), the most prevalent cancer in the north-east of Thailand. A total of 216 /"CCA"/ patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven /"NAT2"/ alleles (/"NAT2"/*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the /"NAT2"/ slow acetylator alleles were not associated with /"CCA"/ risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid /"NAT2"/*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower /"CCA"/ risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the /"NAT2"/ polymorphism may be a modifier of individual risk to /"CCA"/. | [
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15901993 | Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma. | Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA. | Association between genetic polymorphisms of /"CYP1A2"/, arylamine N-acetyltransferase 1 and 2 and susceptibility to /"cholangiocarcinoma"/. | Human /"CYP1A2"/ and arylamine N-acetyltransferases, which are encoded by the polymorphic /"CYP1A2"/ and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between /"CYP1A2"/, NAT1 and NAT2 polymorphisms and /"cholangiocarcinoma"/ (/"CCA"/), the most prevalent cancer in the north-east of Thailand. A total of 216 /"CCA"/ patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two /"CYP1A2"/ alleles (/"CYP1A2"/*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although /"CYP1A2"/*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with /"CCA"/ risk, among the male subjects, the genotype /"CYP1A2"/*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with /"CYP1A2"/*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower /"CCA"/ risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to /"CCA"/. | [
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15901993 | Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma. | Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA. | Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to /"cholangiocarcinoma"/. | Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, /"NAT1"/ and NAT2 polymorphisms and /"cholangiocarcinoma"/ (/"CCA"/), the most prevalent cancer in the north-east of Thailand. A total of 216 /"CCA"/ patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six /"NAT1"/ alleles (/"NAT1"/*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, /"NAT1"/*10 allele, and the NAT2 slow acetylator alleles were not associated with /"CCA"/ risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower /"CCA"/ risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to /"CCA"/. | [
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