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16702373 | Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer. | The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire NBS1 gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within NBS1, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples. | Role of the /"Nijmegen breakage syndrome 1"/ 1"/ gene in familial and sporadic prostate cancer. | The /"Nijmegen breakage syndrome 1"/ 1"/ (/"NBS1"/S1"/) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in /"NBS1"/S1"/, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in /"NBS1"/S1"/ are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire /"NBS1"/S1"/ gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within /"NBS1"/S1"/, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples. | [
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16721725 | Tobacco smoking, NAT2 acetylation genotype and breast cancer risk. | The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers. | Tobacco smoking, /"NAT2"/ acetylation genotype and /"breast cancer"/ risk. | The role of active and passive cigarette smoking in /"breast cancer"/ etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by /"N-acetyl transferase 2"/ (/"NAT2"/) genotype. Women ever exposed to passive smoking at home or at work had a risk of /"breast cancer"/ similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). /"NAT2"/ slow vs. rapid/intermediate acetylation genotype was not related to /"breast cancer"/ risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with /"breast cancer"/ risk; however, active smoking might be associated with an increased risk for early onset /"breast cancers"/. | [
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16721725 | Tobacco smoking, NAT2 acetylation genotype and breast cancer risk. | The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers. | Tobacco smoking, /"NAT2"/ acetylation genotype and breast cancer risk. | The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in /"tumors"/, and the potential modification of the smoking association by /"N-acetyl transferase 2"/ (/"NAT2"/) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and /"ER- tumors"/. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). /"NAT2"/ slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers. | [
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16734939 | Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome. | Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible COMT activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the COMT 158Val/Met polymorphism coding for COMT high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced COMT activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS. | Association of the low-activity /"COMT"/ 158Met allele with ADHD and OCD in subjects with /"velocardiofacial syndrome"/. | /"Velocardiofacial syndrome"/ (/"VCFS"/) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The /"catechol-O-methyltransferase"/ (/"COMT"/), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in /"VCFS"/. Individuals with /"VCFS"/ carrying the low-activity allele (COMTL) are expected to have the lowest possible /"COMT"/ activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in /"VCFS"/. Fifty-five unrelated individuals with /"VCFS"/ underwent psychiatric evaluation and were genotyped for the /"COMT"/ 158Val/Met polymorphism coding for /"COMT"/ high/low-activity alleles. The COMTL allele was significantly more prevalent in /"VCFS"/ subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (/"VCFS"/ subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced /"COMT"/ activity, as expected in /"VCFS"/ COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional /"COMT"/ polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in /"VCFS"/. | [
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16734939 | Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome. | Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible COMT activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the COMT 158Val/Met polymorphism coding for COMT high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced COMT activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS. | Association of the low-activity /"COMT"/ 158Met allele with /"ADHD"/ and OCD in subjects with velocardiofacial syndrome. | Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The /"catechol-O-methyltransferase"/ (/"COMT"/), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible /"COMT"/ activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the /"COMT"/ 158Val/Met polymorphism coding for /"COMT"/ high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with /"attention deficit hyperactivity disorder"/ (/"ADHD"/) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, /"ADHD"/ and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced /"COMT"/ activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional /"COMT"/ polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS. | [
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"text_name": "ADHD"
} | No |
16741941 | Transmission distortion of BDNF variants to bipolar disorder type I patients from a South American population isolate. | Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders. | Transmission distortion of /"BDNF"/ variants to /"bipolar disorder"/ type I patients from a South American population isolate. | Recent reports have implicated polymorphisms in the /"brain derived neurotrophic factor"/ (/"BDNF"/) gene region in the etiology of several psychiatric phenotypes, including /"bipolar disorder"/. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of /"BDNF"/ (Val66Met), an apparently functional variant of this key /"BDNF"/. Here we examined a sample of 224 /"bipolar"/ type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to /"bipolar"/ patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for /"BDNF"/ in susceptibility to mood disorders. | [
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} | {
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"entity_id": "D001714",
"entity_type": "Disease",
"text_name": "bipolar disorder"
} | Yes |
16741941 | Transmission distortion of BDNF variants to bipolar disorder type I patients from a South American population isolate. | Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders. | Transmission distortion of /"BDNF"/ variants to bipolar disorder type I patients from a South American population isolate. | Recent reports have implicated polymorphisms in the /"brain derived neurotrophic factor"/ (/"BDNF"/) gene region in the etiology of several /"psychiatric"/ phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of /"BDNF"/ (Val66Met), an apparently functional variant of this key /"BDNF"/. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for /"BDNF"/ in susceptibility to mood disorders. | [
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} | {
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"entity_id": "D001523",
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"text_name": "psychiatric"
} | No |
16757160 | IL-4 receptor genetic polymorphisms and asthma in Asian populations. | BACKGROUND: IL-4 receptor alpha chain is crucial for the binding and signaling of IL-4, which mediates isotype switching and IgE production. The gene of IL-4 receptor alpha chain is a candidate gene for asthma and atopy. OBJECTIVES: To determine whether Ile50Val and Q576R polymorphisms of IL-4 receptor alpha chain gene were associated with asthma and higher level of total IgE in Chinese, Malay and Indian populations. METHODS: About 303 physician-diagnosed asthmatic subjects (145 Chinese, 73 Malay, 85 Indian) and 355 unselected blood donors (157 Chinese, 98 Malay, 100 Indian) were recruited. Total serum IgE level was measured by ELISA. Genotypes of Ile50/Val and Q576R were determined by PCR and restriction enzyme length polymorphism (RFLP). RESULTS: Ile50Val heterozygote is less frequent in asthmatics than in controls in Malay population (P=0.007). No difference was found in Chinese and Indian population. Ile50/Ile50 was more prevalent in higher total serum IgE group (IgE>100IU/ml) in Malay. The prevalence of Ile50/R576 haplotype was lower in asthmatics than controls in Chinese (P=0.046); while the prevalence of Ile50/Q576 haplotype was lower in asthmatics than in controls in Malay (P=0.048). The frequencies of the two single nucleotide polymorphisms (SNPs) and haplotypes vary among ethnicities (P<0.05). CONCLUSION: IL-4RA gene polymorphisms and its haplotypes showed ethnic variations. The association between IL-4RA gene polymorphisms, its haplotypes and asthma differed from ethnicities. | /"IL-4 receptor"/ genetic polymorphisms and /"asthma"/ in Asian populations. | BACKGROUND: /"IL-4 receptor"/ alpha chain is crucial for the binding and signaling of IL-4, which mediates isotype switching and IgE production. The gene of /"IL-4 receptor"/ alpha chain is a candidate gene for /"asthma"/ and atopy. OBJECTIVES: To determine whether Ile50Val and Q576R polymorphisms of /"IL-4 receptor"/ alpha chain gene were associated with /"asthma"/ and higher level of total IgE in Chinese, Malay and Indian populations. METHODS: About 303 physician-diagnosed asthmatic subjects (145 Chinese, 73 Malay, 85 Indian) and 355 unselected blood donors (157 Chinese, 98 Malay, 100 Indian) were recruited. Total serum IgE level was measured by ELISA. Genotypes of Ile50/Val and Q576R were determined by PCR and restriction enzyme length polymorphism (RFLP). RESULTS: Ile50Val heterozygote is less frequent in asthmatics than in controls in Malay population (P=0.007). No difference was found in Chinese and Indian population. Ile50/Ile50 was more prevalent in higher total serum IgE group (IgE>100IU/ml) in Malay. The prevalence of Ile50/R576 haplotype was lower in asthmatics than controls in Chinese (P=0.046); while the prevalence of Ile50/Q576 haplotype was lower in asthmatics than in controls in Malay (P=0.048). The frequencies of the two single nucleotide polymorphisms (SNPs) and haplotypes vary among ethnicities (P<0.05). CONCLUSION: /"IL-4RA"/ gene polymorphisms and its haplotypes showed ethnic variations. The association between /"IL-4RA"/ gene polymorphisms, its haplotypes and /"asthma"/ differed from ethnicities. | [
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16757160 | IL-4 receptor genetic polymorphisms and asthma in Asian populations. | BACKGROUND: IL-4 receptor alpha chain is crucial for the binding and signaling of IL-4, which mediates isotype switching and IgE production. The gene of IL-4 receptor alpha chain is a candidate gene for asthma and atopy. OBJECTIVES: To determine whether Ile50Val and Q576R polymorphisms of IL-4 receptor alpha chain gene were associated with asthma and higher level of total IgE in Chinese, Malay and Indian populations. METHODS: About 303 physician-diagnosed asthmatic subjects (145 Chinese, 73 Malay, 85 Indian) and 355 unselected blood donors (157 Chinese, 98 Malay, 100 Indian) were recruited. Total serum IgE level was measured by ELISA. Genotypes of Ile50/Val and Q576R were determined by PCR and restriction enzyme length polymorphism (RFLP). RESULTS: Ile50Val heterozygote is less frequent in asthmatics than in controls in Malay population (P=0.007). No difference was found in Chinese and Indian population. Ile50/Ile50 was more prevalent in higher total serum IgE group (IgE>100IU/ml) in Malay. The prevalence of Ile50/R576 haplotype was lower in asthmatics than controls in Chinese (P=0.046); while the prevalence of Ile50/Q576 haplotype was lower in asthmatics than in controls in Malay (P=0.048). The frequencies of the two single nucleotide polymorphisms (SNPs) and haplotypes vary among ethnicities (P<0.05). CONCLUSION: IL-4RA gene polymorphisms and its haplotypes showed ethnic variations. The association between IL-4RA gene polymorphisms, its haplotypes and asthma differed from ethnicities. | /"IL-4 receptor"/ genetic polymorphisms and asthma in Asian populations. | BACKGROUND: /"IL-4 receptor"/ alpha chain is crucial for the binding and signaling of IL-4, which mediates isotype switching and IgE production. The gene of /"IL-4 receptor"/ alpha chain is a candidate gene for asthma and atopy. OBJECTIVES: To determine whether Ile50Val and Q576R polymorphisms of /"IL-4 receptor"/ alpha chain gene were associated with asthma and higher level of total IgE in Chinese, Malay and Indian populations. METHODS: About 303 physician-diagnosed asthmatic subjects (145 Chinese, 73 Malay, 85 Indian) and 355 unselected blood donors (157 Chinese, 98 Malay, 100 Indian) were recruited. Total serum IgE level was measured by ELISA. Genotypes of Ile50/Val and Q576R were determined by PCR and restriction enzyme length polymorphism (RFLP). RESULTS: Ile50Val heterozygote is less frequent in /"asthmatics"/ than in controls in Malay population (P=0.007). No difference was found in Chinese and Indian population. Ile50/Ile50 was more prevalent in higher total serum IgE group (IgE>100IU/ml) in Malay. The prevalence of Ile50/R576 haplotype was lower in /"asthmatics"/ than controls in Chinese (P=0.046); while the prevalence of Ile50/Q576 haplotype was lower in /"asthmatics"/ than in controls in Malay (P=0.048). The frequencies of the two single nucleotide polymorphisms (SNPs) and haplotypes vary among ethnicities (P<0.05). CONCLUSION: /"IL-4RA"/ gene polymorphisms and its haplotypes showed ethnic variations. The association between /"IL-4RA"/ gene polymorphisms, its haplotypes and asthma differed from ethnicities. | [
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16774538 | MMP-1 promoter gene polymorphism and susceptibility to chronic periodontitis in a Chinese population. | A single nucleotide polymorphism in the promoter region of -1607 bp of the human MMP-1 gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis. This study aimed to evaluate the association between the MMP-1 promoter gene polymorphism and chronic periodontitis susceptibility and/or severity in a Chinese population. Genomic DNA was obtained from whole blood samples in 60 Chinese subjects with chronic periodontitis and 50 periodontally healthy subjects as controls. MMP-1 promoter fragment was amplified by polymerase chain reaction, and the polymorphism was analyzed by restriction endonuclease cleavage. In the control subjects, the 2G allele was observed a frequency of 49%, while in severely diseased patients, the 2G allele was seen in 73.4%. The individuals with the 2G allele seem to be approximately three times at greater risk for developing the severe chronic periodontitis (chi(2) = 12.148, P = 0.000). The genotype of 2G/2G was found in 58.5% of the severe periodontitis and 24% of the control group (chi(2) = 11.779, P = 0.003). This study suggests that a single nucleotide polymorphism in the MMP-1 promoter region of -1607 bp may be associated with severe chronic periodontitis in a Chinese population. | /"MMP-1"/ promoter gene polymorphism and susceptibility to chronic periodontitis in a Chinese population. | A single nucleotide polymorphism in the promoter region of -1607 bp of the human /"MMP-1"/ gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis. This study aimed to evaluate the association between the /"MMP-1"/ promoter gene polymorphism and chronic periodontitis susceptibility and/or severity in a Chinese population. Genomic DNA was obtained from whole blood samples in 60 Chinese subjects with chronic periodontitis and 50 periodontally healthy subjects as controls. /"MMP-1"/ promoter fragment was amplified by polymerase chain reaction, and the polymorphism was analyzed by restriction endonuclease cleavage. In the control subjects, the 2G allele was observed a frequency of 49%, while in severely diseased patients, the 2G allele was seen in 73.4%. The individuals with the 2G allele seem to be approximately three times at greater risk for developing the severe chronic periodontitis (chi(2) = 12.148, P = 0.000). The genotype of 2G/2G was found in 58.5% of the severe /"periodontitis"/ and 24% of the control group (chi(2) = 11.779, P = 0.003). This study suggests that a single nucleotide polymorphism in the /"MMP-1"/ promoter region of -1607 bp may be associated with severe chronic periodontitis in a Chinese population. | [
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16774538 | MMP-1 promoter gene polymorphism and susceptibility to chronic periodontitis in a Chinese population. | A single nucleotide polymorphism in the promoter region of -1607 bp of the human MMP-1 gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis. This study aimed to evaluate the association between the MMP-1 promoter gene polymorphism and chronic periodontitis susceptibility and/or severity in a Chinese population. Genomic DNA was obtained from whole blood samples in 60 Chinese subjects with chronic periodontitis and 50 periodontally healthy subjects as controls. MMP-1 promoter fragment was amplified by polymerase chain reaction, and the polymorphism was analyzed by restriction endonuclease cleavage. In the control subjects, the 2G allele was observed a frequency of 49%, while in severely diseased patients, the 2G allele was seen in 73.4%. The individuals with the 2G allele seem to be approximately three times at greater risk for developing the severe chronic periodontitis (chi(2) = 12.148, P = 0.000). The genotype of 2G/2G was found in 58.5% of the severe periodontitis and 24% of the control group (chi(2) = 11.779, P = 0.003). This study suggests that a single nucleotide polymorphism in the MMP-1 promoter region of -1607 bp may be associated with severe chronic periodontitis in a Chinese population. | /"MMP-1"/ promoter gene polymorphism and susceptibility to /"chronic periodontitis"/ in a Chinese population. | A single nucleotide polymorphism in the promoter region of -1607 bp of the human /"MMP-1"/ gene has been found to be associated with an increased risk of various inflammatory diseases and cancer metastasis. This study aimed to evaluate the association between the /"MMP-1"/ promoter gene polymorphism and /"chronic periodontitis"/ susceptibility and/or severity in a Chinese population. Genomic DNA was obtained from whole blood samples in 60 Chinese subjects with /"chronic periodontitis"/ and 50 periodontally healthy subjects as controls. /"MMP-1"/ promoter fragment was amplified by polymerase chain reaction, and the polymorphism was analyzed by restriction endonuclease cleavage. In the control subjects, the 2G allele was observed a frequency of 49%, while in severely diseased patients, the 2G allele was seen in 73.4%. The individuals with the 2G allele seem to be approximately three times at greater risk for developing the severe /"chronic periodontitis"/ (chi(2) = 12.148, P = 0.000). The genotype of 2G/2G was found in 58.5% of the severe periodontitis and 24% of the control group (chi(2) = 11.779, P = 0.003). This study suggests that a single nucleotide polymorphism in the /"MMP-1"/ promoter region of -1607 bp may be associated with severe /"chronic periodontitis"/ in a Chinese population. | [
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16775186 | Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II Nutrition Cohort. | Paraoxonase 1 (PON1) plays an important role in the high-density lipoprotein-mediated prevention of low-density lipoprotein oxidation and the metabolism of lipid-soluble radicals. In this study, we investigated the association of two common, nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M) with breast cancer risk in postmenopausal women through a nested case-control study within the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Using conditional logistic regression of genotyping results from 502 cases and 502 cancer-free controls matched on age, race/ethnicity, and date of blood draw, we found that the L55M single nucleotide polymorphism (SNP) was associated with an increased risk of breast cancer [odds ratio (OR), 1.58; 95% confidence interval (95% CI), 1.05-2.37 for MM]. No association was found for the Q192R SNP. The L55M association with breast cancer was modified by nonsteroidal anti-inflammatory drug (NSAID) use. The association was limited to women who took NSAIDs and was somewhat stronger among women who reported regular (> or = 15 times per month) NSAID use (OR, 3.24; 95% CI, 1.17-9.00) than in those who reported any NSAID use (OR, 2.46; 95% CI, 1.39-4.36). These results suggest that genetic variation in PON1, particularly at the L55M SNP, may be associated with increased risk of breast cancer in postmenopausal women. Furthermore, NSAID use seems to modify this risk. | Association of polymorphisms in the /"paraoxonase 1"/ gene with /"breast cancer"/ incidence in the CPS-II Nutrition Cohort. | /"Paraoxonase 1"/ (/"PON1"/) plays an important role in the high-density lipoprotein-mediated prevention of low-density lipoprotein oxidation and the metabolism of lipid-soluble radicals. In this study, we investigated the association of two common, nonsynonymous polymorphisms in the /"PON1"/ gene (Q192R and L55M) with /"breast cancer"/ risk in postmenopausal women through a nested case-control study within the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Using conditional logistic regression of genotyping results from 502 cases and 502 cancer-free controls matched on age, race/ethnicity, and date of blood draw, we found that the L55M single nucleotide polymorphism (SNP) was associated with an increased risk of /"breast cancer"/ [odds ratio (OR), 1.58; 95% confidence interval (95% CI), 1.05-2.37 for MM]. No association was found for the Q192R SNP. The L55M association with /"breast cancer"/ was modified by nonsteroidal anti-inflammatory drug (NSAID) use. The association was limited to women who took NSAIDs and was somewhat stronger among women who reported regular (> or = 15 times per month) NSAID use (OR, 3.24; 95% CI, 1.17-9.00) than in those who reported any NSAID use (OR, 2.46; 95% CI, 1.39-4.36). These results suggest that genetic variation in /"PON1"/, particularly at the L55M SNP, may be associated with increased risk of /"breast cancer"/ in postmenopausal women. Furthermore, NSAID use seems to modify this risk. | [
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} | Yes |
16775186 | Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II Nutrition Cohort. | Paraoxonase 1 (PON1) plays an important role in the high-density lipoprotein-mediated prevention of low-density lipoprotein oxidation and the metabolism of lipid-soluble radicals. In this study, we investigated the association of two common, nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M) with breast cancer risk in postmenopausal women through a nested case-control study within the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Using conditional logistic regression of genotyping results from 502 cases and 502 cancer-free controls matched on age, race/ethnicity, and date of blood draw, we found that the L55M single nucleotide polymorphism (SNP) was associated with an increased risk of breast cancer [odds ratio (OR), 1.58; 95% confidence interval (95% CI), 1.05-2.37 for MM]. No association was found for the Q192R SNP. The L55M association with breast cancer was modified by nonsteroidal anti-inflammatory drug (NSAID) use. The association was limited to women who took NSAIDs and was somewhat stronger among women who reported regular (> or = 15 times per month) NSAID use (OR, 3.24; 95% CI, 1.17-9.00) than in those who reported any NSAID use (OR, 2.46; 95% CI, 1.39-4.36). These results suggest that genetic variation in PON1, particularly at the L55M SNP, may be associated with increased risk of breast cancer in postmenopausal women. Furthermore, NSAID use seems to modify this risk. | Association of polymorphisms in the /"paraoxonase 1"/ gene with breast cancer incidence in the CPS-II Nutrition Cohort. | /"Paraoxonase 1"/ (/"PON1"/) plays an important role in the high-density lipoprotein-mediated prevention of low-density lipoprotein oxidation and the metabolism of lipid-soluble radicals. In this study, we investigated the association of two common, nonsynonymous polymorphisms in the /"PON1"/ gene (Q192R and L55M) with breast cancer risk in postmenopausal women through a nested case-control study within the American /"Cancer"/ Society /"Cancer"/ Prevention Study II Nutrition Cohort. Using conditional logistic regression of genotyping results from 502 cases and 502 /"cancer"/-free controls matched on age, race/ethnicity, and date of blood draw, we found that the L55M single nucleotide polymorphism (SNP) was associated with an increased risk of breast cancer [odds ratio (OR), 1.58; 95% confidence interval (95% CI), 1.05-2.37 for MM]. No association was found for the Q192R SNP. The L55M association with breast cancer was modified by nonsteroidal anti-inflammatory drug (NSAID) use. The association was limited to women who took NSAIDs and was somewhat stronger among women who reported regular (> or = 15 times per month) NSAID use (OR, 3.24; 95% CI, 1.17-9.00) than in those who reported any NSAID use (OR, 2.46; 95% CI, 1.39-4.36). These results suggest that genetic variation in /"PON1"/, particularly at the L55M SNP, may be associated with increased risk of breast cancer in postmenopausal women. Furthermore, NSAID use seems to modify this risk. | [
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16788379 | Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk. | OBJECTIVE: Endogenous and exogenous estrogens influence breast cancer risk by interacting with estrogen receptor (ER). The O-methylguanine DNA methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and in inhibiting ER-mediated cell proliferation. We assessed the two MGMT polymorphisms, Leu84Phe and Ile143Val, with breast cancer risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on breast cancer risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on breast cancer risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of MGMT to inhibit estrogen receptor-mediated cell proliferation and is associated with breast cancer risk. | Polymorphisms in /"O6-methylguanine DNA methyltransferase"/ and /"breast cancer"/ risk. | OBJECTIVE: Endogenous and exogenous estrogens influence /"breast cancer"/ risk by interacting with estrogen receptor (ER). The /"O-methylguanine DNA methyltransferase"/ (/"MGMT"/) gene has a dual role in repairing alkylation damage and in inhibiting ER-mediated cell proliferation. We assessed the two /"MGMT"/ polymorphisms, Leu84Phe and Ile143Val, with /"breast cancer"/ risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on /"breast cancer"/ risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on /"breast cancer"/ risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of /"MGMT"/ to inhibit estrogen receptor-mediated cell proliferation and is associated with /"breast cancer"/ risk. | [
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16788379 | Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk. | OBJECTIVE: Endogenous and exogenous estrogens influence breast cancer risk by interacting with estrogen receptor (ER). The O-methylguanine DNA methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and in inhibiting ER-mediated cell proliferation. We assessed the two MGMT polymorphisms, Leu84Phe and Ile143Val, with breast cancer risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on breast cancer risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on breast cancer risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of MGMT to inhibit estrogen receptor-mediated cell proliferation and is associated with breast cancer risk. | Polymorphisms in O6-methylguanine DNA methyltransferase and /"breast cancer"/ risk. | OBJECTIVE: Endogenous and exogenous estrogens influence /"breast cancer"/ risk by interacting with /"estrogen receptor"/ (/"ER"/). The O-methylguanine DNA methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and in inhibiting /"ER"/-mediated cell proliferation. We assessed the two MGMT polymorphisms, Leu84Phe and Ile143Val, with /"breast cancer"/ risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on /"breast cancer"/ risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly /"estrogen receptor"/-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on /"breast cancer"/ risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of MGMT to inhibit /"estrogen receptor"/-mediated cell proliferation and is associated with /"breast cancer"/ risk. | [
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16796743 | Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | Evidence for the association of the SLC22A4 and /"SLC22A5"/ genes with type 1 diabetes: a case control study. | BACKGROUND: /"Type 1 diabetes"/ (/"T1D"/) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in /"T1D"/ patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and /"SLC22A5"/ genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with /"T1D"/ of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, /"OCTN2"/-promoter and /"OCTN2"/-intron. METHODS: A case-control study was performed in the Spanish population with 295 /"T1D"/ patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with /"T1D"/ in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for /"T1D"/ (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between /"T1D"/ patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in /"T1D"/ risk. | [
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} | Yes |
16796743 | Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | Evidence for the association of the /"SLC22A4"/ and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: /"Type 1 diabetes"/ (/"T1D"/) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in /"T1D"/ patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the /"SLC22A4"/ and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with /"T1D"/ of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 /"T1D"/ patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the /"SLC22A4"/ gene at 1672 showed significant association with /"T1D"/ in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for /"T1D"/ (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between /"T1D"/ patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in /"T1D"/ risk. | [
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16796743 | Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | Evidence for the association of the SLC22A4 and /"SLC22A5"/ genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and /"SLC22A5"/ genes, have been involved in susceptibility to two other autoimmune diseases, /"rheumatoid arthritis"/ and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, /"OCTN2"/-promoter and /"OCTN2"/-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | [
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16796743 | Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | Evidence for the association of the /"SLC22A4"/ and SLC22A5 genes with type 1 diabetes: a case control study. | BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the /"SLC22A4"/ and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and /"Crohn's disease"/. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the /"SLC22A4"/ gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk. | [
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16797247 | Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. | BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between UGT1A6 variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the prevention of colorectal cancer have not been studied extensively. METHODS: UGT1A6 and CYP2C9 genotypes were determined in 2295 individuals with colorectal cancer and 2903 controls. Interactions between these genotypes, aspirin or ibuprofen use, and colorectal cancer risk were determined. RESULTS: Variant CYP2C9 genotypes enhanced the protective effect of ibuprofen on the prevention of colorectal cancer, and a dose-response relationship with respect to increasing numbers of variant alleles was seen (P interaction = .02). CYP2C9 variants were more effective in individuals with wild-type rather than variant UGT1A6 (P interaction < .007). Variant CYP2C9 genotypes showed no interaction with aspirin usage, and variant UGT1A6 genotypes showed no interaction with either NSAID with respect to colorectal cancer protection. CONCLUSIONS: In this study, the major effect seen was an enhancement by slower-metabolizing CYP2C9 variants of the chemopreventive activity of ibuprofen against colorectal cancer. | Interactions between /"CYP2C9"/ and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in /"colorectal cancer"/ prevention. | BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between UGT1A6 variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), /"cytochrome P4502C9"/ (/"CYP2C9"/), and NSAIDs in the prevention of /"colorectal cancer"/ have not been studied extensively. METHODS: UGT1A6 and /"CYP2C9"/ genotypes were determined in 2295 individuals with /"colorectal cancer"/ and 2903 controls. Interactions between these genotypes, aspirin or ibuprofen use, and /"colorectal cancer"/ risk were determined. RESULTS: Variant /"CYP2C9"/ genotypes enhanced the protective effect of ibuprofen on the prevention of /"colorectal cancer"/, and a dose-response relationship with respect to increasing numbers of variant alleles was seen (P interaction = .02). /"CYP2C9"/ variants were more effective in individuals with wild-type rather than variant UGT1A6 (P interaction < .007). Variant /"CYP2C9"/ genotypes showed no interaction with aspirin usage, and variant UGT1A6 genotypes showed no interaction with either NSAID with respect to /"colorectal cancer"/ protection. CONCLUSIONS: In this study, the major effect seen was an enhancement by slower-metabolizing /"CYP2C9"/ variants of the chemopreventive activity of ibuprofen against /"colorectal cancer"/. | [
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16797247 | Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. | BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between UGT1A6 variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the prevention of colorectal cancer have not been studied extensively. METHODS: UGT1A6 and CYP2C9 genotypes were determined in 2295 individuals with colorectal cancer and 2903 controls. Interactions between these genotypes, aspirin or ibuprofen use, and colorectal cancer risk were determined. RESULTS: Variant CYP2C9 genotypes enhanced the protective effect of ibuprofen on the prevention of colorectal cancer, and a dose-response relationship with respect to increasing numbers of variant alleles was seen (P interaction = .02). CYP2C9 variants were more effective in individuals with wild-type rather than variant UGT1A6 (P interaction < .007). Variant CYP2C9 genotypes showed no interaction with aspirin usage, and variant UGT1A6 genotypes showed no interaction with either NSAID with respect to colorectal cancer protection. CONCLUSIONS: In this study, the major effect seen was an enhancement by slower-metabolizing CYP2C9 variants of the chemopreventive activity of ibuprofen against colorectal cancer. | Interactions between CYP2C9 and /"UGT1A6"/ polymorphisms and nonsteroidal anti-inflammatory drugs in /"colorectal cancer"/ prevention. | BACKGROUND AND AIMS: Variant genotypes of /"uridine diphosphate glucuronsyltransferase isoenzyme 1A6"/ (/"UGT1A6"/) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between /"UGT1A6"/ variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the prevention of /"colorectal cancer"/ have not been studied extensively. METHODS: /"UGT1A6"/ and CYP2C9 genotypes were determined in 2295 individuals with /"colorectal cancer"/ and 2903 controls. Interactions between these genotypes, aspirin or ibuprofen use, and /"colorectal cancer"/ risk were determined. RESULTS: Variant CYP2C9 genotypes enhanced the protective effect of ibuprofen on the prevention of /"colorectal cancer"/, and a dose-response relationship with respect to increasing numbers of variant alleles was seen (P interaction = .02). CYP2C9 variants were more effective in individuals with wild-type rather than variant /"UGT1A6"/ (P interaction < .007). Variant CYP2C9 genotypes showed no interaction with aspirin usage, and variant /"UGT1A6"/ genotypes showed no interaction with either NSAID with respect to /"colorectal cancer"/ protection. CONCLUSIONS: In this study, the major effect seen was an enhancement by slower-metabolizing CYP2C9 variants of the chemopreventive activity of ibuprofen against /"colorectal cancer"/. | [
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} | No |
16802107 | Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder? | We present the third case of Niemann-Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann-Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann-Pick disease type C (NPC). To verify the histopathological findings, SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann-Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. | Subclinical course of adult visceral /"Niemann-Pick type C1 disease"/. A rare or underdiagnosed disorder? | We present the third case of /"Niemann-Pick disease type C"/ without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann-Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of /"Niemann-Pick disease type C"/ (/"NPC"/). To verify the histopathological findings, SMPD1, /"NPC1"/ and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the /"NPC1"/ gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both /"NPC1"/ variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of /"Niemann-Pick disease type C"/, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of /"NPC"/ should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. | [
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16802107 | Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder? | We present the third case of Niemann-Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann-Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann-Pick disease type C (NPC). To verify the histopathological findings, SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann-Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. | Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder? | We present the third case of Niemann-Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, /"lymphadenopathy"/ and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann-Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann-Pick disease type C (NPC). To verify the histopathological findings, /"SMPD1"/, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the /"SMPD1"/ gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann-Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, /"DRD2"/, DRD3, and DRD4, and dopamine transporter) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors /"DRD1"/, DRD2, DRD3, and DRD4, and dopamine transporter) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, /"DRD3"/, and DRD4, and dopamine transporter) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of /"DRD4"/ 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and /"DRD4"/, and dopamine transporter) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of /"DRD4"/ gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and /"dopamine transporter"/) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and /"dopamine transporter"/) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and /"dopamine transporter"/) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16816977 | Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent. | Genetic susceptibility to /"Parkinson's disease"/ among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker. | The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of /"Parkinson's disease"/ (/"PD"/). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic /"PD"/. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and /"dopamine transporter"/) with /"PD"/ among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with /"PD"/ was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with /"PD"/ in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with /"PD"/ from the Indian sub-continent. | [
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16821592 | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer. | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced /"ovarian cancer"/. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced /"ovarian cancer"/ (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and /"LRP"/ in 60 advanced /"ovarian cancer"/ patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced /"ovarian cancer"/. | [
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16821592 | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer. | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced /"ovarian cancer"/. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced /"ovarian cancer"/ (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for /"MDR1"/, MRP1, MRP2 and LRP in 60 advanced /"ovarian cancer"/ patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced /"ovarian cancer"/. | [
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16821592 | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer. | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced /"ovarian cancer"/. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced /"ovarian cancer"/ (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, /"MRP1"/, MRP2 and LRP in 60 advanced /"ovarian cancer"/ patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding /"MRP1"/ exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced /"ovarian cancer"/. | [
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16821592 | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer. | Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced /"ovarian cancer"/. | BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced /"ovarian cancer"/ (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, /"MRP2"/ and LRP in 60 advanced /"ovarian cancer"/ patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced /"ovarian cancer"/. | [
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16824064 | Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. | BACKGROUND AND AIM: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking. | Interleukin-8 gene polymorphism associated with susceptibility to non-cardia /"gastric carcinoma"/ with microsatellite instability. | BACKGROUND AND AIM: /"Gastric carcinoma"/ (/"GC"/) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) /"GC"/. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia /"GC"/. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with /"GC"/, interleukin (IL)-8 -251, /"IL-1B"/-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in /"GC"/ cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) /"GC"/ cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of /"MSI-H GC"/ compared to /"MSI-L/MSS GC"/ and controls. We found no association between other cytokine polymorphisms and /"MSI-H GC"/. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than /"MSI-L/MSS GC"/. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that /"MSI-H GC"/ is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking. | [
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16824064 | Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. | BACKGROUND AND AIM: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking. | /"Interleukin-8"/ gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. | BACKGROUND AND AIM: Gastric carcinoma (GC) with microsatellite instability (/"MSI"/) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of /"MSI"/ remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and /"MSI"/ phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of /"MSI"/ and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of /"MSI"/ (MSI-H and /"MSI-L"/) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that /"IL-8"/ -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that MSI-H GC is associated with /"IL-8"/-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking. | [
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16855621 | Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations with rheumatoid arthritis. | The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility. | Microsatellite typing for /"DRB1"/ alleles: application to the analysis of HLA associations with /"rheumatoid arthritis"/. | The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for /"DRB1"/ genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 /"RA"/ patients and 374 controls) and 1364 Korean individuals (744 /"RA"/ patients and 620 controls), all of whom were previously genotyped for /"DRB1"/. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of /"DRB1"/*09 and /"DRB1"/*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with /"rheumatoid arthritis"/, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility. | [
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16860143 | Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. | Mutations of the perforin gene (PRF1) are present in a proportion of patients with hemophagocytic lymphohistiocytosis (HLH). We found that all identified infants with HLH of African descent (17 from USA, 4 from Europe) have 50delT-PRF1 (16 homozygotes, 5 compound heterozygotes), accounting for the most frequently observed PRF1 mutation. Two additional patients with HLH, self-reporting as Hispanic, carried 50delT, but no Caucasians were identified with 50delT. To test the hypothesis that this mutation represents a single haplotype, DNA from 23 patients with HLH and 30 African-American control subjects was sequenced for the PRF1 gene, including portions of the intron containing known single nucleotide polymorphisms (SNPs). The same groups were genotyped at 3 microsatellites proximal to PRF1. The SNP profiles of patients with 50delT-PRF1 were identical, and 5 novel SNPs were identified among African-American control subjects. Patients with 50delT-PRF1 were also found to have had an earlier age of disease onset than patients with other PRF1 mutations. Extent of haplotype sharing and variability of microsatellite alleles in 50delT-PRF1 chromosomes suggest that this mutation arose approximately 1000 to 4000 years ago and is restricted to patients of African descent. | Patients of African ancestry with /"hemophagocytic lymphohistiocytosis"/ share a common haplotype of /"PRF1"/ with a 50delT mutation. | Mutations of the perforin gene (/"PRF1"/) are present in a proportion of patients with /"hemophagocytic lymphohistiocytosis"/ (/"HLH"/). We found that all identified infants with /"HLH"/ of African descent (17 from USA, 4 from Europe) have 50delT-/"PRF1"/ (16 homozygotes, 5 compound heterozygotes), accounting for the most frequently observed /"PRF1"/ mutation. Two additional patients with /"HLH"/, self-reporting as Hispanic, carried 50delT, but no Caucasians were identified with 50delT. To test the hypothesis that this mutation represents a single haplotype, DNA from 23 patients with /"HLH"/ and 30 African-American control subjects was sequenced for the /"PRF1"/ gene, including portions of the intron containing known single nucleotide polymorphisms (SNPs). The same groups were genotyped at 3 microsatellites proximal to /"PRF1"/. The SNP profiles of patients with 50delT-/"PRF1"/ were identical, and 5 novel SNPs were identified among African-American control subjects. Patients with 50delT-/"PRF1"/ were also found to have had an earlier age of disease onset than patients with other /"PRF1"/ mutations. Extent of haplotype sharing and variability of microsatellite alleles in 50delT-/"PRF1"/ chromosomes suggest that this mutation arose approximately 1000 to 4000 years ago and is restricted to patients of African descent. | [
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16882462 | Apolipoprotein E genotype and gallbladder disease risk in a large population-based cohort. | PURPOSE: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and gallbladder disease incidence. METHODS: Cases of incident hospitalized gallbladder disease were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for gallbladder disease. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized gallbladder disease associated with the presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with epsilon4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57). CONCLUSIONS: These results suggest that independent of traditional risk factors, apoE genotype may influence gallbladder disease risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation. | /"Apolipoprotein E"/ genotype and /"gallbladder disease"/ risk in a large population-based cohort. | PURPOSE: The aim of the study is to describe the association between /"apolipoprotein E"/ (/"apoE"/) genotype and /"gallbladder disease"/ incidence. METHODS: Cases of incident hospitalized /"gallbladder disease"/ were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for /"gallbladder disease"/. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized /"gallbladder disease"/ associated with the presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with epsilon4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for /"gallbladder disease"/ (relative risk, 1.28; 95% CI, 1.05-1.57). CONCLUSIONS: These results suggest that independent of traditional risk factors, /"apoE"/ genotype may influence /"gallbladder disease"/ risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation. | [
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] | {
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} | {
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"entity_type": "Disease",
"text_name": "gallbladder disease"
} | Yes |
16882462 | Apolipoprotein E genotype and gallbladder disease risk in a large population-based cohort. | PURPOSE: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and gallbladder disease incidence. METHODS: Cases of incident hospitalized gallbladder disease were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for gallbladder disease. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized gallbladder disease associated with the presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with epsilon4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57). CONCLUSIONS: These results suggest that independent of traditional risk factors, apoE genotype may influence gallbladder disease risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation. | Apolipoprotein E genotype and /"gallbladder disease"/ risk in a large population-based cohort. | PURPOSE: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and /"gallbladder disease"/ incidence. METHODS: Cases of incident hospitalized /"gallbladder disease"/ were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for /"gallbladder disease"/. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized /"gallbladder disease"/ associated with the presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with epsilon4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e., genotypes /"E2/2, E2/3"/, and E2/4 versus others) was associated with a modest increased risk for /"gallbladder disease"/ (relative risk, 1.28; 95% CI, 1.05-1.57). CONCLUSIONS: These results suggest that independent of traditional risk factors, apoE genotype may influence /"gallbladder disease"/ risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation. | [
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} | No |
16909243 | WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls, associations and renal phenotypes. | WT1 mutations have been considered a rare cause of nephrotic syndrome but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to nephrotic syndrome since they do not respond to drugs. We screened for WT1 mutations in 200 patients with nephrotic syndrome: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of nephrotic syndrome (NPHS2, CD2AP) had been previously excluded. Three girls out of 32 of the group with steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. WT1 hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy. | /"WT1"/ mutations in /"nephrotic syndrome"/ revisited. High prevalence in young girls, associations and renal phenotypes. | /"WT1"/ mutations have been considered a rare cause of /"nephrotic syndrome"/ but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to /"nephrotic syndrome"/ since they do not respond to drugs. We screened for /"WT1"/ mutations in 200 patients with /"nephrotic syndrome"/: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of /"nephrotic syndrome"/ (NPHS2, CD2AP) had been previously excluded. Three girls out of 32 of the group with steroid resistance under 18 years presented classical /"WT1"/ splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, /"WT1"/ splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. /"WT1"/ hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy. | [
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} | Yes |
16909243 | WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls, associations and renal phenotypes. | WT1 mutations have been considered a rare cause of nephrotic syndrome but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to nephrotic syndrome since they do not respond to drugs. We screened for WT1 mutations in 200 patients with nephrotic syndrome: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of nephrotic syndrome (NPHS2, CD2AP) had been previously excluded. Three girls out of 32 of the group with steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. WT1 hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy. | WT1 mutations in /"nephrotic syndrome"/ revisited. High prevalence in young girls, associations and renal phenotypes. | WT1 mutations have been considered a rare cause of /"nephrotic syndrome"/ but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to /"nephrotic syndrome"/ since they do not respond to drugs. We screened for WT1 mutations in 200 patients with /"nephrotic syndrome"/: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of /"nephrotic syndrome"/ (/"NPHS2"/, CD2AP) had been previously excluded. Three girls out of 32 of the group with steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. WT1 hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy. | [
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"entity_type": "Disease",
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16911713 | Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with endometriosis. | To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed endometriosis and 114 healthy women. Distributions of two single-base polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ significantly among control and endometriosis (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of endometriosis [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against endometriosis development. | Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with /"endometriosis"/. | To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic /"endometriosis"/. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed /"endometriosis"/ and 114 healthy women. Distributions of two single-base polymorphisms of the human /"interleukin-1 receptor type I"/ (/"IL-1RI"/) gene were evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ significantly among control and /"endometriosis"/ (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of /"endometriosis"/ [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against /"endometriosis"/ development. | [
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"entity_id": "D004715",
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"text_name": "endometriosis"
} | Yes |
16911713 | Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with endometriosis. | To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed endometriosis and 114 healthy women. Distributions of two single-base polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ significantly among control and endometriosis (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of endometriosis [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against endometriosis development. | Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with /"endometriosis"/. | To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic /"endometriosis"/. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed /"endometriosis"/ and 114 healthy women. Distributions of two single-base polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were evaluated: /"PstI"/, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for /"PstI"/ polymorphisms did not differ significantly among control and /"endometriosis"/ (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of /"endometriosis"/ [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against /"endometriosis"/ development. | [
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} | No |
16917940 | Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children. | Dopamine D4 receptor (DRD4) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with ADHD. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between ADHD and DRD4 gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DRD4 gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between ADHD and DRD4 gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with ADHD (P = 0.01) in the case-control analysis. We concluded that ADHD is not associated with a particular VNTR polymorphism of the DRD4 gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the DRD4 gene in the pathogenesis of ADHD. | Exon 3 polymorphisms of /"dopamine D4 receptor"/ (/"DRD4"/) gene and /"attention deficit hyperactivity disorder"/ in Chinese children. | /"Dopamine D4 receptor"/ (/"DRD4"/) gene is implicated in the pathogenesis of /"attention deficit hyperactivity disorder"/ (/"ADHD"/). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with /"ADHD"/. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between /"ADHD"/ and /"DRD4"/ gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with /"ADHD"/ by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the /"DRD4"/ gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four /"ADHD"/ cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between /"ADHD"/ and /"DRD4"/ gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with /"ADHD"/ (P = 0.01) in the case-control analysis. We concluded that /"ADHD"/ is not associated with a particular VNTR polymorphism of the /"DRD4"/ gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the /"DRD4"/ gene in the pathogenesis of /"ADHD"/. | [
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16917940 | Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children. | Dopamine D4 receptor (DRD4) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with ADHD. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between ADHD and DRD4 gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DRD4 gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between ADHD and DRD4 gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with ADHD (P = 0.01) in the case-control analysis. We concluded that ADHD is not associated with a particular VNTR polymorphism of the DRD4 gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the DRD4 gene in the pathogenesis of ADHD. | Exon 3 polymorphisms of /"dopamine D4 receptor"/ (/"DRD4"/) gene and attention deficit hyperactivity disorder in Chinese children. | /"Dopamine D4 receptor"/ (/"DRD4"/) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with ADHD. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between ADHD and /"DRD4"/ gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, /"mental retardation"/, or neurological deficits. VNTR polymorphisms of the /"DRD4"/ gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between ADHD and /"DRD4"/ gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with ADHD (P = 0.01) in the case-control analysis. We concluded that ADHD is not associated with a particular VNTR polymorphism of the /"DRD4"/ gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the /"DRD4"/ gene in the pathogenesis of ADHD. | [
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16930377 | Considering the causes of RLS. | The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and transferrin in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of RLS remains unclear. | Considering the causes of /"RLS"/. | The pathophysiology of /"restless legs syndrome"/ (/"RLS"/) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary /"RLS"/, such as pregnancy or end-stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with /"RLS"/ have normal serum ferritin levels, concentrations of ferritin and /"transferrin"/ in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of /"RLS"/. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of /"RLS"/ remains unclear. | [
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} | Yes |
16930377 | Considering the causes of RLS. | The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and transferrin in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of RLS remains unclear. | Considering the causes of RLS. | The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterized by /"iron deficiency"/, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and /"transferrin"/ in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of RLS remains unclear. | [
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16932953 | The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. | OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The MDR1 gene product, P-glycoprotein (P-gp), is probably one of the most important and best defined transporters for drug delivery in humans. P-gp transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T MDR1 gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T MDR1 gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs. | The effect of 3435C>T /"MDR1"/ gene polymorphism on /"rheumatoid arthritis"/ treatment with disease-modifying antirheumatic drugs. | OBJECTIVE: /"Rheumatoid arthritis"/ (/"RA"/) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of /"RA"/ is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The /"MDR1"/ gene product, /"P-glycoprotein"/ (/"P-gp"/), is probably one of the most important and best defined transporters for drug delivery in humans. /"P-gp"/ transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T /"MDR1"/ gene polymorphism on the efficacy of /"RA"/ treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with /"RA"/ treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of /"RA symptoms"/ after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of /"RA symptoms"/ in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T /"MDR1"/ gene polymorphism may influence the efficacy of /"RA"/ therapy with disease-modifying antirheumatic drugs. | [
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"text_name": "rheumatoid arthritis"
} | Yes |
16932953 | The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. | OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The MDR1 gene product, P-glycoprotein (P-gp), is probably one of the most important and best defined transporters for drug delivery in humans. P-gp transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T MDR1 gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T MDR1 gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs. | The effect of 3435C>T /"MDR1"/ gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. | OBJECTIVE: Rheumatoid arthritis (RA) is a /"multifactorial disease"/, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The /"MDR1"/ gene product, /"P-glycoprotein"/ (/"P-gp"/), is probably one of the most important and best defined transporters for drug delivery in humans. /"P-gp"/ transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T /"MDR1"/ gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T /"MDR1"/ gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs. | [
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} | No |
16945136 | Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer. | Gene x Gene interaction between MnSOD and /"GPX-1"/ and /"breast cancer"/ risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of /"breast cancer"/. However, these mutations are rare in the general population, and account for little of the incidence of /"sporadic breast cancer"/ in the general population. Therefore, research has been focused on examining associations between common polymorphisms and /"breast cancer"/ risk. To date, few associations have been described. This has led to the hypothesis that /"breast cancer"/ is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (/"GPX-1"/) genes have been proposed as low penetrance alleles, and have not been clearly associated with /"breast cancer"/. We investigated whether variants at both polymorphisms, while not independently associated with /"breast cancer"/ risk, could influence /"breast cancer"/ risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with /"breast cancer"/ to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and /"GPX-1"/ (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in /"breast cancer"/ risk, an increase in the risk of /"breast cancer"/ (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of /"GPX-1"/. CONCLUSION: Polymorphisms in the /"GPX-1"/ and MnSOD genes are associated with an increased risk of /"breast cancer"/. | [
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"text_name": "sporadic breast cancer"
} | Yes |
16945136 | Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer. | Gene x Gene interaction between /"MnSOD"/ and GPX-1 and /"breast cancer"/ risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of /"breast cancer"/. However, these mutations are rare in the general population, and account for little of the incidence of /"sporadic breast cancer"/ in the general population. Therefore, research has been focused on examining associations between common polymorphisms and /"breast cancer"/ risk. To date, few associations have been described. This has led to the hypothesis that /"breast cancer"/ is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the /"manganese superoxide dismutase"/ (/"MnSOD"/) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with /"breast cancer"/. We investigated whether variants at both polymorphisms, while not independently associated with /"breast cancer"/ risk, could influence /"breast cancer"/ risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with /"breast cancer"/ to 1533 disease free women. The /"MnSOD"/ (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in /"breast cancer"/ risk, an increase in the risk of /"breast cancer"/ (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of /"MnSOD"/ and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and /"MnSOD"/ genes are associated with an increased risk of /"breast cancer"/. | [
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16945136 | Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer. | Gene x Gene interaction between MnSOD and GPX-1 and /"breast cancer"/ risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, /"BRCA2"/, and ATM can cause a substantial increase in risk of /"breast cancer"/. However, these mutations are rare in the general population, and account for little of the incidence of /"sporadic breast cancer"/ in the general population. Therefore, research has been focused on examining associations between common polymorphisms and /"breast cancer"/ risk. To date, few associations have been described. This has led to the hypothesis that /"breast cancer"/ is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with /"breast cancer"/. We investigated whether variants at both polymorphisms, while not independently associated with /"breast cancer"/ risk, could influence /"breast cancer"/ risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with /"breast cancer"/ to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in /"breast cancer"/ risk, an increase in the risk of /"breast cancer"/ (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of /"breast cancer"/. | [
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16945136 | Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer. | Gene x Gene interaction between MnSOD and GPX-1 and /"breast cancer"/ risk: a nested case-control study. | BACKGROUND: Germ-line mutations in genes such as BRCA1, /"BRCA2"/, and ATM can cause a substantial increase in risk of /"breast cancer"/. However, these mutations are rare in the general population, and account for little of the incidence of /"sporadic breast cancer"/ in the general population. Therefore, research has been focused on examining associations between common polymorphisms and /"breast cancer"/ risk. To date, few associations have been described. This has led to the hypothesis that /"breast cancer"/ is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with /"breast cancer"/. We investigated whether variants at both polymorphisms, while not independently associated with /"breast cancer"/ risk, could influence /"breast cancer"/ risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with /"breast cancer"/ to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in /"breast cancer"/ risk, an increase in the risk of /"breast cancer"/ (OR 1.87, 95% CI 1.09 - 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of /"breast cancer"/. | [
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16956834 | ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia. | The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | /"ET-1"/ and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with /"sickle cell anemia"/. | The association of /"endothelin 1"/ (/"ET-1"/) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that /"ET-1"/ T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | [
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16956834 | ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia. | The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | ET-1 and /"ecNOS"/ gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with /"sickle cell anemia"/. | The association of endothelin 1 (ET-1) and /"endothelial constitutive nitric oxide synthase"/ (/"ecNOS"/) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and /"ecNOS"/ C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | [
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16956834 | ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia. | The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | ET-1 and /"ecNOS"/ gene polymorphisms andsusceptibility to /"acute chest syndrome"/ and painful vaso-occlusive crises in children with sickle cell anemia. | The association of endothelin 1 (ET-1) and /"endothelial constitutive nitric oxide synthase"/ (/"ecNOS"/) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of /"acute chest syndrome"/ and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and /"ecNOS"/ C-786 alleles are associated with, respectively, an increased and a decreased risk of /"acute chest syndrome"/. | [
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16956834 | ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia. | The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome. | /"ET-1"/ and ecNOS gene polymorphisms andsusceptibility to /"acute chest syndrome"/ and painful vaso-occlusive crises in children with sickle cell anemia. | The association of /"endothelin 1"/ (/"ET-1"/) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of /"acute chest syndrome"/ and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that /"ET-1"/ T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of /"acute chest syndrome"/. | [
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17005168 | GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | /"GSTT1"/ and GSTM1 allelic polymorphisms in /"head and neck cancer"/ patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (/"GSTT1"/) is currently controversial. The present study investigates the prevalences of /"GSTT1"/ and GSTM1 polymorphism in a cohort of 100 /"head and neck cancer"/ patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of /"GSTT1"/ and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between /"head and neck cancer"/ and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with /"GSTT1"/ null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | [
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17005168 | GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | GSTT1 and /"GSTM1"/ allelic polymorphisms in /"head and neck cancer"/ patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of /"glutathione S-transferase M1"/ (/"GSTM1"/) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and /"GSTM1"/ polymorphism in a cohort of 100 /"head and neck cancer"/ patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and /"GSTM1"/ genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between /"head and neck cancer"/ and /"GSTM1"/ null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of /"GSTM1"/ detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | [
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17005168 | GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | /"GSTT1"/ and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between /"head and neck squamous cell carcinoma"/ (/"HNSCC"/) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (/"GSTT1"/) is currently controversial. The present study investigates the prevalences of /"GSTT1"/ and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of /"GSTT1"/ and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with /"GSTT1"/ null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of /"HNSCC"/ in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | [
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17005168 | GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | /"GSTT1"/ and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region. | BACKGROUND: The association between /"head and neck squamous cell carcinoma"/ (/"HNSCC"/) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (/"GSTT1"/) is currently controversial. The present study investigates the prevalences of /"GSTT1"/ and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of /"GSTT1"/ and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with /"GSTT1"/ null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of /"HNSCC"/ in patients from the Italian Lazio Region, independently of age, sex and other confounding variables. | [
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17006606 | A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. | Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression. | A polymorphism of C-to-T substitution at -31 /"IL1B"/ is associated with the risk of advanced /"gastric adenocarcinoma"/ in a Japanese population. | Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with /"gastric cancer"/ risk, of which /"IL1B"/-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the /"IL1B"/ transcription. The signal transduction target upon /"interleukin 1 beta"/ (/"IL1beta"/) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese /"gastric cancer"/ patients were affected by the /"IL1B"/ -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident /"gastric adenocarcinoma"/ patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in /"IL1B"/ in both the cases and controls (R (2)=0.94). Neither /"IL1B"/-31, -511 nor FAS-670 polymorphisms showed significantly different risks of /"gastric adenocarcinoma"/. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with /"IL1B"/-31TT (or /"IL1B"/-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either /"IL1B"/-31TT (or /"IL1B"/-511CC) genotype compared with stage I subjects. These observations suggest that /"IL1B"/-31TT and /"IL1B"/-511CC are associated with disease progression. | [
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17006606 | A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. | Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression. | A polymorphism of C-to-T substitution at -31 /"IL1B"/ is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. | Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which /"IL1B"/-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the /"IL1B"/ transcription. The signal transduction target upon /"interleukin 1 beta"/ (/"IL1beta"/) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports /"cancer"/ development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on /"cancer"/ development, we sought to determine if Japanese gastric cancer patients were affected by the /"IL1B"/ -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in /"IL1B"/ in both the cases and controls (R (2)=0.94). Neither /"IL1B"/-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with /"IL1B"/-31TT (or /"IL1B"/-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either /"IL1B"/-31TT (or /"IL1B"/-511CC) genotype compared with stage I subjects. These observations suggest that /"IL1B"/-31TT and /"IL1B"/-511CC are associated with disease progression. | [
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17036313 | V37I connexin 26 allele in patients with sensorineural hearing loss: evidence of its pathogenicity. | Sensorineural hearing loss (SNHL) is the most common inherited sensory disorder, reported in 1-3 of every 1,000 births. It has been estimated that 50% of all cases of prelingual SNHL are genetically determined. There is tremendous genetic heterogeneity, with multiple dominant and recessive loci. Mutations of the gap junction beta-2 gene (GJB2) emerge as a leading cause of autosomal recessive non-syndromic SNHL. Over 90 sequence alterations have been reported, the pathogenicity of some of them being unknown or unclear. The status of the V37I allele of connexin 26 (GJB2 amino acid product) with regards to its association with SNHL has been controversial. This study examines the pathogenicity of V37I by comparing the frequency of this allele in 40 patients with SNHL of Chinese and Caucasian descent with the frequency of the allele in 100 anonymized, ethnically matched controls. The V37I allele was identified in 43.75 and 11.5% of the patient and control alleles of Chinese ethnicity, respectively, but was not found in either Caucasian cohort. We also compiled the audiograms of 15 individuals with SNHL homozygous for the V37I allele, and showed that these individuals present with a mild to moderate SNHL. These results indicate that (1) the V37I allele is common in individuals of Chinese descent but rarely present in individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but produces milder hearing loss compared to nonsense mutations of connexin 26 such as the 35delG mutation. | V37I /"connexin 26"/ allele in patients with /"sensorineural hearing loss"/: evidence of its pathogenicity. | /"Sensorineural hearing loss"/ (/"SNHL"/) is the most common inherited sensory disorder, reported in 1-3 of every 1,000 births. It has been estimated that 50% of all cases of prelingual /"SNHL"/ are genetically determined. There is tremendous genetic heterogeneity, with multiple dominant and recessive loci. Mutations of the gap junction beta-2 gene (/"GJB2"/) emerge as a leading cause of autosomal recessive non-syndromic SNHL. Over 90 sequence alterations have been reported, the pathogenicity of some of them being unknown or unclear. The status of the V37I allele of /"connexin 26"/ (/"GJB2"/ amino acid product) with regards to its association with /"SNHL"/ has been controversial. This study examines the pathogenicity of V37I by comparing the frequency of this allele in 40 patients with /"SNHL"/ of Chinese and Caucasian descent with the frequency of the allele in 100 anonymized, ethnically matched controls. The V37I allele was identified in 43.75 and 11.5% of the patient and control alleles of Chinese ethnicity, respectively, but was not found in either Caucasian cohort. We also compiled the audiograms of 15 individuals with /"SNHL"/ homozygous for the V37I allele, and showed that these individuals present with a mild to moderate /"SNHL"/. These results indicate that (1) the V37I allele is common in individuals of Chinese descent but rarely present in individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but produces milder hearing loss compared to nonsense mutations of /"connexin 26"/ such as the 35delG mutation. | [
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17036313 | V37I connexin 26 allele in patients with sensorineural hearing loss: evidence of its pathogenicity. | Sensorineural hearing loss (SNHL) is the most common inherited sensory disorder, reported in 1-3 of every 1,000 births. It has been estimated that 50% of all cases of prelingual SNHL are genetically determined. There is tremendous genetic heterogeneity, with multiple dominant and recessive loci. Mutations of the gap junction beta-2 gene (GJB2) emerge as a leading cause of autosomal recessive non-syndromic SNHL. Over 90 sequence alterations have been reported, the pathogenicity of some of them being unknown or unclear. The status of the V37I allele of connexin 26 (GJB2 amino acid product) with regards to its association with SNHL has been controversial. This study examines the pathogenicity of V37I by comparing the frequency of this allele in 40 patients with SNHL of Chinese and Caucasian descent with the frequency of the allele in 100 anonymized, ethnically matched controls. The V37I allele was identified in 43.75 and 11.5% of the patient and control alleles of Chinese ethnicity, respectively, but was not found in either Caucasian cohort. We also compiled the audiograms of 15 individuals with SNHL homozygous for the V37I allele, and showed that these individuals present with a mild to moderate SNHL. These results indicate that (1) the V37I allele is common in individuals of Chinese descent but rarely present in individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but produces milder hearing loss compared to nonsense mutations of connexin 26 such as the 35delG mutation. | V37I /"connexin 26"/ allele in patients with sensorineural hearing loss: evidence of its pathogenicity. | Sensorineural hearing loss (SNHL) is the most common inherited sensory disorder, reported in 1-3 of every 1,000 births. It has been estimated that 50% of all cases of prelingual SNHL are genetically determined. There is tremendous genetic heterogeneity, with multiple dominant and recessive loci. Mutations of the gap junction beta-2 gene (/"GJB2"/) emerge as a leading cause of /"autosomal recessive non-syndromic SNHL"/. Over 90 sequence alterations have been reported, the pathogenicity of some of them being unknown or unclear. The status of the V37I allele of /"connexin 26"/ (/"GJB2"/ amino acid product) with regards to its association with SNHL has been controversial. This study examines the pathogenicity of V37I by comparing the frequency of this allele in 40 patients with SNHL of Chinese and Caucasian descent with the frequency of the allele in 100 anonymized, ethnically matched controls. The V37I allele was identified in 43.75 and 11.5% of the patient and control alleles of Chinese ethnicity, respectively, but was not found in either Caucasian cohort. We also compiled the audiograms of 15 individuals with SNHL homozygous for the V37I allele, and showed that these individuals present with a mild to moderate SNHL. These results indicate that (1) the V37I allele is common in individuals of Chinese descent but rarely present in individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but produces milder hearing loss compared to nonsense mutations of /"connexin 26"/ such as the 35delG mutation. | [
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17039310 | SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis. | To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis. | /"SAA1"/ gene polymorphisms and the risk of /"AA amyloidosis"/ in Japanese patients with rheumatoid arthritis. | To investigate the precise modality of association between /"SAA1"/ gene polymorphisms and the development of /"AA amyloidosis"/ in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having /"amyloidosis"/, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without /"amyloidosis"/. Possible associations between these SNPs and /"amyloidosis"/ were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of /"AA amyloidosis"/. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with /"amyloidosis"/, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with /"amyloidosis"/. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of /"amyloidosis"/. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of /"amyloidosis"/. | [
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17039310 | SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis. | To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis. | SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with /"rheumatoid arthritis"/. | To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with /"rheumatoid arthritis"/ (/"RA"/), Japanese patients with /"RA"/ (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the /"SAA"/ gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis. | [
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17040410 | Serotonin transporter gene polymorphism and irritable bowel syndrome. | Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT) gene may underlie the disturbance in gut function in patients with irritable bowel syndrome (IBS). Association studies of SERT polymorphisms and IBS have shown diverse results among different countries, which might be due to racial and subject composition differences. The aim of this study was to assess the potential association between SERT polymorphisms and IBS in Koreans. A total of 190 IBS patients, who met the Rome II criteria, and 437 healthy controls were subjected to genotyping. SERT polymorphisms differed in the IBS and control groups (P = 0.014). The SERT deletion/deletion genotype occurred with greater frequency in the diarrhoea-predominant IBS group than in the controls. A strong genotypic association was observed between the SERT deletion/deletion genotype and diarrhoea-predominant IBS (P = 0.012). None of the clinical symptoms analysed was significantly associated with the SERT genotypes. The frequency of the SERT insertion/insertion genotype was much lower than that of the other two genotypes. A significant association was observed between the SERT polymorphism and IBS, especially diarrhoea-predominant IBS, suggesting that the SERT gene is a potential candidate gene involved in IBS in Korea. | /"Serotonin transporter"/ gene polymorphism and /"irritable bowel syndrome"/. | Polymorphisms in the promoter region of the /"serotonin reuptake transporter"/ (/"SERT"/) gene may underlie the disturbance in gut function in patients with /"irritable bowel syndrome"/ (/"IBS"/). Association studies of /"SERT"/ polymorphisms and /"IBS"/ have shown diverse results among different countries, which might be due to racial and subject composition differences. The aim of this study was to assess the potential association between /"SERT"/ polymorphisms and /"IBS"/ in Koreans. A total of 190 /"IBS"/ patients, who met the Rome II criteria, and 437 healthy controls were subjected to genotyping. /"SERT"/ polymorphisms differed in the /"IBS"/ and control groups (P = 0.014). The /"SERT"/ deletion/deletion genotype occurred with greater frequency in the diarrhoea-predominant /"IBS"/ group than in the controls. A strong genotypic association was observed between the /"SERT"/ deletion/deletion genotype and diarrhoea-predominant /"IBS"/ (P = 0.012). None of the clinical symptoms analysed was significantly associated with the /"SERT"/ genotypes. The frequency of the /"SERT"/ insertion/insertion genotype was much lower than that of the other two genotypes. A significant association was observed between the /"SERT"/ polymorphism and /"IBS"/, especially diarrhoea-predominant /"IBS"/, suggesting that the /"SERT"/ gene is a potential candidate gene involved in /"IBS"/ in Korea. | [
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17040410 | Serotonin transporter gene polymorphism and irritable bowel syndrome. | Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT) gene may underlie the disturbance in gut function in patients with irritable bowel syndrome (IBS). Association studies of SERT polymorphisms and IBS have shown diverse results among different countries, which might be due to racial and subject composition differences. The aim of this study was to assess the potential association between SERT polymorphisms and IBS in Koreans. A total of 190 IBS patients, who met the Rome II criteria, and 437 healthy controls were subjected to genotyping. SERT polymorphisms differed in the IBS and control groups (P = 0.014). The SERT deletion/deletion genotype occurred with greater frequency in the diarrhoea-predominant IBS group than in the controls. A strong genotypic association was observed between the SERT deletion/deletion genotype and diarrhoea-predominant IBS (P = 0.012). None of the clinical symptoms analysed was significantly associated with the SERT genotypes. The frequency of the SERT insertion/insertion genotype was much lower than that of the other two genotypes. A significant association was observed between the SERT polymorphism and IBS, especially diarrhoea-predominant IBS, suggesting that the SERT gene is a potential candidate gene involved in IBS in Korea. | /"Serotonin transporter"/ gene polymorphism and irritable bowel syndrome. | Polymorphisms in the promoter region of the /"serotonin reuptake transporter"/ (/"SERT"/) gene may underlie the disturbance in gut function in patients with irritable bowel syndrome (IBS). Association studies of /"SERT"/ polymorphisms and IBS have shown diverse results among different countries, which might be due to racial and subject composition differences. The aim of this study was to assess the potential association between /"SERT"/ polymorphisms and IBS in Koreans. A total of 190 IBS patients, who met the Rome II criteria, and 437 healthy controls were subjected to genotyping. /"SERT"/ polymorphisms differed in the IBS and control groups (P = 0.014). The /"SERT"/ deletion/deletion genotype occurred with greater frequency in the /"diarrhoea"/-predominant IBS group than in the controls. A strong genotypic association was observed between the /"SERT"/ deletion/deletion genotype and /"diarrhoea"/-predominant IBS (P = 0.012). None of the clinical symptoms analysed was significantly associated with the /"SERT"/ genotypes. The frequency of the /"SERT"/ insertion/insertion genotype was much lower than that of the other two genotypes. A significant association was observed between the /"SERT"/ polymorphism and IBS, especially /"diarrhoea"/-predominant IBS, suggesting that the /"SERT"/ gene is a potential candidate gene involved in IBS in Korea. | [
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17044097 | Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples. | Brain-derived neurotrophic factor (BDNF) plays an important role in normal neuronal development. Several lines of evidence implicate the involvement of BDNF in attention-deficit hyperactivity disorder (ADHD). This study investigated the role of two common BDNF variants (Val66Met, C270T) in two samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212). We found evidence of increased transmission of the C allele of the C270T in Taiwanese samples (TDT: chi(2) = 6.78, P = 0.009) and the two samples pooled together (TDT: chi(2) = 7.24, P = 0.007). No association was found between the Val66Met polymorphism and ADHD in either of the two populations. Analysis of haplotypes demonstrated a significant decreased transmission of haplotypes containing the Val66 allele and the 270T allele in the Taiwanese samples (TDT: chi(2) = 4.57, P = 0.032) and the pooled sample set (TDT: chi(2) = 5.82, P = 0.016). This study provides evidence for the possible involvement of BDNF in susceptibility to ADHD. | Family-based association study between /"brain-derived neurotrophic factor"/ gene polymorphisms and attention /"deficit hyperactivity disorder"/ in UK and Taiwanese samples. | /"Brain-derived neurotrophic factor"/ (/"BDNF"/) plays an important role in normal neuronal development. Several lines of evidence implicate the involvement of /"BDNF"/ in /"attention-deficit hyperactivity disorder"/ (/"ADHD"/). This study investigated the role of two common /"BDNF"/ variants (Val66Met, C270T) in two samples of /"ADHD"/ probands from the United Kingdom (n = 180) and Taiwan (n = 212). We found evidence of increased transmission of the C allele of the C270T in Taiwanese samples (TDT: chi(2) = 6.78, P = 0.009) and the two samples pooled together (TDT: chi(2) = 7.24, P = 0.007). No association was found between the Val66Met polymorphism and /"ADHD"/ in either of the two populations. Analysis of haplotypes demonstrated a significant decreased transmission of haplotypes containing the Val66 allele and the 270T allele in the Taiwanese samples (TDT: chi(2) = 4.57, P = 0.032) and the pooled sample set (TDT: chi(2) = 5.82, P = 0.016). This study provides evidence for the possible involvement of /"BDNF"/ in susceptibility to /"ADHD"/. | [
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17050201 | Synergistic effect of arsenic trioxide and flt3 inhibition on cells with flt3 internal tandem duplication. | Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). Flt3-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in AML cells. In this study, we aimed to clarify whether ATO and Flt3 inhibition would be a more specific and efficient therapy for Flt3-ITD cells. We demonstrate that the combination of ATO and an Flt3 inhibitor, AG1296, profoundly inhibits the growth of Flt3-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in Flt3-ITD cells (BaF3-Flt3-ITD, MV4-11, and PL-21 cells), but not in Flt3 wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for Flt3-ITD cells that involves combined treatment with Flt3 inhibitors and ATO. | Synergistic effect of arsenic trioxide and /"flt3"/ inhibition on cells with /"flt3"/ internal tandem duplication. | /"Flt3"/ internal tandem duplication (/"Flt3"/-ITD) is a prevalent mutation in /"acute myeloid leukemia"/ (/"AML"/). /"Flt3"/-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in /"AML"/ cells. In this study, we aimed to clarify whether ATO and /"Flt3"/ inhibition would be a more specific and efficient therapy for /"Flt3"/-ITD cells. We demonstrate that the combination of ATO and an /"Flt3"/ inhibitor, AG1296, profoundly inhibits the growth of /"Flt3"/-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in /"Flt3"/-ITD cells (BaF3-/"Flt3"/-ITD, MV4-11, and PL-21 cells), but not in /"Flt3"/ wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for /"Flt3"/-ITD cells that involves combined treatment with /"Flt3"/ inhibitors and ATO. | [
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} | {
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"text_name": "acute myeloid leukemia"
} | Yes |
17050201 | Synergistic effect of arsenic trioxide and flt3 inhibition on cells with flt3 internal tandem duplication. | Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). Flt3-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in AML cells. In this study, we aimed to clarify whether ATO and Flt3 inhibition would be a more specific and efficient therapy for Flt3-ITD cells. We demonstrate that the combination of ATO and an Flt3 inhibitor, AG1296, profoundly inhibits the growth of Flt3-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in Flt3-ITD cells (BaF3-Flt3-ITD, MV4-11, and PL-21 cells), but not in Flt3 wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for Flt3-ITD cells that involves combined treatment with Flt3 inhibitors and ATO. | Synergistic effect of arsenic trioxide and flt3 inhibition on cells with flt3 internal tandem duplication. | Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in /"acute myeloid leukemia"/ (/"AML"/). Flt3-ITD constitutively activates various signaling pathways, including a /"mitogen-activated protein kinase kinase"/ (/"MEK"/)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and /"MEK"/ inhibition were recently reported to interact synergistically to induce apoptosis in /"AML"/ cells. In this study, we aimed to clarify whether ATO and Flt3 inhibition would be a more specific and efficient therapy for Flt3-ITD cells. We demonstrate that the combination of ATO and an Flt3 inhibitor, AG1296, profoundly inhibits the growth of Flt3-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in Flt3-ITD cells (BaF3-Flt3-ITD, MV4-11, and PL-21 cells), but not in Flt3 wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for Flt3-ITD cells that involves combined treatment with Flt3 inhibitors and ATO. | [
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"text_name": "AML"
} | No |
17054105 | Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome. | Activating mutations in v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been identified as the molecular cause underlying Costello syndrome (CS). To further investigate the phenotypic spectrum associated with germline HRAS mutations and characterize their molecular diversity, subjects with a diagnosis of CS (N = 9), Noonan syndrome (NS; N = 36), cardiofaciocutaneous syndrome (CFCS; N = 4), or with a phenotype suggestive of these conditions but without a definitive diagnosis (N = 12) were screened for the entire coding sequence of the gene. A de novo heterozygous HRAS change was detected in all the subjects diagnosed with CS, while no lesion was observed with any of the other phenotypes. While eight cases shared the recurrent c.34G>A change, a novel c.436G>A transition was observed in one individual. The latter affected residue, p.Ala146, which contributes to guanosine triphosphate (GTP)/guanosine diphosphate (GDP) binding, defining a novel class of activating HRAS lesions that perturb development. Clinical characterization indicated that p.Gly12Ser was associated with a homogeneous phenotype. By analyzing the genomic region flanking the HRAS mutations, we traced the parental origin of lesions in nine informative families and demonstrated that de novo mutations were inherited from the father in all cases. We noted an advanced age at conception in unaffected fathers transmitting the mutation. | Diversity, parental germline origin, and phenotypic spectrum of de novo /"HRAS"/ missense changes in /"Costello syndrome"/. | Activating mutations in v-Ha-ras Harvey rat sarcoma viral oncogene homolog (/"HRAS"/) have recently been identified as the molecular cause underlying /"Costello syndrome"/ (/"CS"/). To further investigate the phenotypic spectrum associated with germline /"HRAS"/ mutations and characterize their molecular diversity, subjects with a diagnosis of /"CS"/ (N = 9), Noonan syndrome (NS; N = 36), cardiofaciocutaneous syndrome (CFCS; N = 4), or with a phenotype suggestive of these conditions but without a definitive diagnosis (N = 12) were screened for the entire coding sequence of the gene. A de novo heterozygous /"HRAS"/ change was detected in all the subjects diagnosed with /"CS"/, while no lesion was observed with any of the other phenotypes. While eight cases shared the recurrent c.34G>A change, a novel c.436G>A transition was observed in one individual. The latter affected residue, p.Ala146, which contributes to guanosine triphosphate (GTP)/guanosine diphosphate (GDP) binding, defining a novel class of activating /"HRAS"/ lesions that perturb development. Clinical characterization indicated that p.Gly12Ser was associated with a homogeneous phenotype. By analyzing the genomic region flanking the /"HRAS"/ mutations, we traced the parental origin of lesions in nine informative families and demonstrated that de novo mutations were inherited from the father in all cases. We noted an advanced age at conception in unaffected fathers transmitting the mutation. | [
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} | Yes |
17054105 | Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome. | Activating mutations in v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been identified as the molecular cause underlying Costello syndrome (CS). To further investigate the phenotypic spectrum associated with germline HRAS mutations and characterize their molecular diversity, subjects with a diagnosis of CS (N = 9), Noonan syndrome (NS; N = 36), cardiofaciocutaneous syndrome (CFCS; N = 4), or with a phenotype suggestive of these conditions but without a definitive diagnosis (N = 12) were screened for the entire coding sequence of the gene. A de novo heterozygous HRAS change was detected in all the subjects diagnosed with CS, while no lesion was observed with any of the other phenotypes. While eight cases shared the recurrent c.34G>A change, a novel c.436G>A transition was observed in one individual. The latter affected residue, p.Ala146, which contributes to guanosine triphosphate (GTP)/guanosine diphosphate (GDP) binding, defining a novel class of activating HRAS lesions that perturb development. Clinical characterization indicated that p.Gly12Ser was associated with a homogeneous phenotype. By analyzing the genomic region flanking the HRAS mutations, we traced the parental origin of lesions in nine informative families and demonstrated that de novo mutations were inherited from the father in all cases. We noted an advanced age at conception in unaffected fathers transmitting the mutation. | Diversity, parental germline origin, and phenotypic spectrum of de novo /"HRAS"/ missense changes in Costello syndrome. | Activating mutations in v-Ha-ras Harvey rat sarcoma viral oncogene homolog (/"HRAS"/) have recently been identified as the molecular cause underlying Costello syndrome (CS). To further investigate the phenotypic spectrum associated with germline /"HRAS"/ mutations and characterize their molecular diversity, subjects with a diagnosis of CS (N = 9), /"Noonan syndrome"/ (/"NS"/; N = 36), cardiofaciocutaneous syndrome (CFCS; N = 4), or with a phenotype suggestive of these conditions but without a definitive diagnosis (N = 12) were screened for the entire coding sequence of the gene. A de novo heterozygous /"HRAS"/ change was detected in all the subjects diagnosed with CS, while no lesion was observed with any of the other phenotypes. While eight cases shared the recurrent c.34G>A change, a novel c.436G>A transition was observed in one individual. The latter affected residue, p.Ala146, which contributes to guanosine triphosphate (GTP)/guanosine diphosphate (GDP) binding, defining a novel class of activating /"HRAS"/ lesions that perturb development. Clinical characterization indicated that p.Gly12Ser was associated with a homogeneous phenotype. By analyzing the genomic region flanking the /"HRAS"/ mutations, we traced the parental origin of lesions in nine informative families and demonstrated that de novo mutations were inherited from the father in all cases. We noted an advanced age at conception in unaffected fathers transmitting the mutation. | [
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} | No |
17067442 | Are carriers for MEFV mutations "healthy"? | OBJECTIVE: We aimed to compare whether carriers for the MEFV mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with FMF and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, rheumatoid arthritis, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with FMF were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, rheumatoid arthritis and prophylaxis of penicillin, acute rheumatic fever, and rheumatoid arthritis were significantly higher in asymptomatic parents for the MEFV mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one MEFV mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for MEFV mutations seem to be unique, in that they cause an alteration in the state of "health". | Are carriers for /"MEFV"/ mutations "healthy"? | OBJECTIVE: We aimed to compare whether carriers for the /"MEFV"/ mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with /"FMF"/ and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, rheumatoid arthritis, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with /"FMF"/ were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, rheumatoid arthritis and prophylaxis of penicillin, acute rheumatic fever, and rheumatoid arthritis were significantly higher in asymptomatic parents for the /"MEFV"/ mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one /"MEFV"/ mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for /"MEFV"/ mutations seem to be unique, in that they cause an alteration in the state of "health". | [
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"text_name": "spondyloarthropathy"
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17067442 | Are carriers for MEFV mutations "healthy"? | OBJECTIVE: We aimed to compare whether carriers for the MEFV mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with FMF and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, rheumatoid arthritis, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with FMF were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, rheumatoid arthritis and prophylaxis of penicillin, acute rheumatic fever, and rheumatoid arthritis were significantly higher in asymptomatic parents for the MEFV mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one MEFV mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for MEFV mutations seem to be unique, in that they cause an alteration in the state of "health". | Are carriers for /"MEFV"/ mutations "healthy"? | OBJECTIVE: We aimed to compare whether carriers for the /"MEFV"/ mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with FMF and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, /"rheumatoid arthritis"/, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with FMF were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, /"rheumatoid arthritis"/ and prophylaxis of penicillin, acute rheumatic fever, and /"rheumatoid arthritis"/ were significantly higher in asymptomatic parents for the /"MEFV"/ mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one /"MEFV"/ mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for /"MEFV"/ mutations seem to be unique, in that they cause an alteration in the state of "health". | [
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} | No |
17082176 | Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study. | NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens. | Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study. | /"NADP(H):quinone oxidoreductase 1"/ (/"NQO1"/) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with /"colorectal neoplasia"/ because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with /"colorectal carcinogenesis"/. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The /"NQO1"/ 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens. | [
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} | Yes |
17082176 | Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study. | NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens. | Role of NQO1C609T and /"EPHX1"/ gene polymorphisms in the association of smoking and alcohol with sporadic distal /"colorectal adenomas"/: results from the UKFSS Study. | NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (/"EPHX1"/, also /"mEH"/) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal /"colorectal adenomas"/ in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and /"colorectal adenoma"/ was modified by NQO1C609T genotype, such that the relation between alcohol and /"colorectal adenoma"/ was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and /"colorectal adenoma risk"/ and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of /"colorectal adenomas"/. Alcohol increases risk of /"colorectal adenoma"/ in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens. | [
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} | No |
17094469 | MDM2 T309G polymorphism is associated with bladder cancer. | Recently, a functional T to G polymorphism at nucleotide 309 in the promoter region of the MDM2 gene (rs: 2279744, SNP 309) has been identified. This polymorphism has an impact on the expression of the MDM2 gene, which is a key negative regulator of the tumor suppressor molecule p53. The effect of T309G polymorphism of the MDM2 gene on bladder cancer susceptibility was investigated in a case-control study of 75 bladder cancer patients and 103 controls from Turkey. The G/G genotype exhibited an increased risk of 2.68 (95% CI, 1.34-5.40) for bladder cancer compared with the combination of low-risk genotypes T/T and T/G at this locus. These results show an association between MDM2 T309G polymorphism and bladder cancer in our study group. To the best of our knowledge, this is the first study reporting that MDM2 T309G polymorphism may be a potential genetic susceptibility factor for bladder cancer. | /"MDM2"/ T309G polymorphism is associated with /"bladder cancer"/. | Recently, a functional T to G polymorphism at nucleotide 309 in the promoter region of the /"MDM2"/ gene (rs: 2279744, SNP 309) has been identified. This polymorphism has an impact on the expression of the /"MDM2"/ gene, which is a key negative regulator of the tumor suppressor molecule p53. The effect of T309G polymorphism of the /"MDM2"/ gene on /"bladder cancer"/ susceptibility was investigated in a case-control study of 75 /"bladder cancer"/ patients and 103 controls from Turkey. The G/G genotype exhibited an increased risk of 2.68 (95% CI, 1.34-5.40) for /"bladder cancer"/ compared with the combination of low-risk genotypes T/T and T/G at this locus. These results show an association between /"MDM2"/ T309G polymorphism and /"bladder cancer"/ in our study group. To the best of our knowledge, this is the first study reporting that /"MDM2"/ T309G polymorphism may be a potential genetic susceptibility factor for /"bladder cancer"/. | [
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17094469 | MDM2 T309G polymorphism is associated with bladder cancer. | Recently, a functional T to G polymorphism at nucleotide 309 in the promoter region of the MDM2 gene (rs: 2279744, SNP 309) has been identified. This polymorphism has an impact on the expression of the MDM2 gene, which is a key negative regulator of the tumor suppressor molecule p53. The effect of T309G polymorphism of the MDM2 gene on bladder cancer susceptibility was investigated in a case-control study of 75 bladder cancer patients and 103 controls from Turkey. The G/G genotype exhibited an increased risk of 2.68 (95% CI, 1.34-5.40) for bladder cancer compared with the combination of low-risk genotypes T/T and T/G at this locus. These results show an association between MDM2 T309G polymorphism and bladder cancer in our study group. To the best of our knowledge, this is the first study reporting that MDM2 T309G polymorphism may be a potential genetic susceptibility factor for bladder cancer. | MDM2 T309G polymorphism is associated with /"bladder cancer"/. | Recently, a functional T to G polymorphism at nucleotide 309 in the promoter region of the MDM2 gene (rs: 2279744, SNP 309) has been identified. This polymorphism has an impact on the expression of the MDM2 gene, which is a key negative regulator of the tumor suppressor molecule /"p53"/. The effect of T309G polymorphism of the MDM2 gene on /"bladder cancer"/ susceptibility was investigated in a case-control study of 75 /"bladder cancer"/ patients and 103 controls from Turkey. The G/G genotype exhibited an increased risk of 2.68 (95% CI, 1.34-5.40) for /"bladder cancer"/ compared with the combination of low-risk genotypes T/T and T/G at this locus. These results show an association between MDM2 T309G polymorphism and /"bladder cancer"/ in our study group. To the best of our knowledge, this is the first study reporting that MDM2 T309G polymorphism may be a potential genetic susceptibility factor for /"bladder cancer"/. | [
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17095747 | A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. | RATIONALE: Genetic variation influences susceptibility to clinical tuberculosis (TB). Activation of the P2X(7) receptor on human macrophages induces killing of mycobacteria. We have identified polymorphisms in the P2X(7) gene that markedly reduce this killing. OBJECTIVE: To determine if polymorphisms in P2X7 are associated with increased risk of TB, the prevalence of four polymorphisms was assessed in individuals from Southeast Asia, where the majority of patients with TB in our study originate. The association of these polymorphisms with clinical TB was subsequently investigated in two separate case-control cohorts and the function of P2X(7) was assessed in subjects from one cohort. METHODS: Genotyping of P2X7 polymorphisms was performed from subjects in a nested case-control study of a longitudinal refugee cohort and a separate case-control study. The functional capacity of P2X(7) was investigated by measuring ATP-mediated mycobacterial killing and apoptosis. RESULTS: Only the 1513A-C polymorphism was present in Southeast Asians and the allele was associated with reduced killing of Mycobacterium tuberculosis. The 1513C allele was strongly associated with extrapulmonary, but not pulmonary, TB in the first (odds ratio, 3.8; 95% confidence interval, 1.6-9.0) and second cohorts (odds ratio, 3.7; 95% confidence interval, 1.7-8.0). ATP-mediated killing of mycobacteria was ablated in macrophages from subjects homozygous for the 1513C allele and significantly impaired in macrophages from heterozygous subjects. There was strong correlation between the degree of mycobacterial killing and ATP-induced apoptosis. CONCLUSIONS: The 1513C allele increases susceptibility to extrapulmonary TB, and this defect is associated with the reduction in the capacity of macrophages to kill M. tuberculosis. | A polymorphism in the /"P2X7"/ gene increases susceptibility to /"extrapulmonary tuberculosis"/. | RATIONALE: Genetic variation influences susceptibility to clinical /"tuberculosis"/ (/"TB"/). Activation of the /"P2X(7) receptor"/ on human macrophages induces killing of mycobacteria. We have identified polymorphisms in the /"P2X(7)"/ gene that markedly reduce this killing. OBJECTIVE: To determine if polymorphisms in /"P2X7"/ are associated with increased risk of /"TB"/, the prevalence of four polymorphisms was assessed in individuals from Southeast Asia, where the majority of patients with /"TB"/ in our study originate. The association of these polymorphisms with clinical /"TB"/ was subsequently investigated in two separate case-control cohorts and the function of /"P2X(7)"/ was assessed in subjects from one cohort. METHODS: Genotyping of /"P2X7"/ polymorphisms was performed from subjects in a nested case-control study of a longitudinal refugee cohort and a separate case-control study. The functional capacity of /"P2X(7)"/ was investigated by measuring ATP-mediated mycobacterial killing and apoptosis. RESULTS: Only the 1513A-C polymorphism was present in Southeast Asians and the allele was associated with reduced killing of Mycobacterium /"tuberculosis"/. The 1513C allele was strongly associated with extrapulmonary, but not pulmonary, /"TB"/ in the first (odds ratio, 3.8; 95% confidence interval, 1.6-9.0) and second cohorts (odds ratio, 3.7; 95% confidence interval, 1.7-8.0). ATP-mediated killing of mycobacteria was ablated in macrophages from subjects homozygous for the 1513C allele and significantly impaired in macrophages from heterozygous subjects. There was strong correlation between the degree of mycobacterial killing and ATP-induced apoptosis. CONCLUSIONS: The 1513C allele increases susceptibility to extrapulmonary /"TB"/, and this defect is associated with the reduction in the capacity of macrophages to kill M. /"tuberculosis"/. | [
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17102945 | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF. | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and /"MEFV"/ mutations to amyloidosis and course of the disease in the patients with /"familial Mediterranean fever"/er"/. | OBJECTIVE: To evaluate the effects of /"MEFV"/ genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of /"familial Mediterranean fever"/er"/ (/"FMF"/MF"/) and amyloidosis in a group of Turkish /"FMF"/MF"/ patients. METHODS: We evaluated 105 adult /"FMF"/MF"/ patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of /"FMF"/MF"/ or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the /"MEFV"/ gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the /"MEFV"/ genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in /"FMF"/MF"/. | [
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17102945 | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF. | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and /"MEFV"/ mutations to /"amyloidosis"/ and course of the disease in the patients with /"familial Mediterranean fever"/. | OBJECTIVE: To evaluate the effects of /"MEFV"/ genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of /"familial Mediterranean fever"/ (/"FMF"/) and /"amyloidosis"/ in a group of Turkish /"FMF"/ patients. METHODS: We evaluated 105 adult /"FMF"/ patients (with or without /"amyloidosis"/, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of /"FMF"/ or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the /"MEFV"/ gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and /"amyloidosis"/ were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the /"amyloidosis"/ development. However, when we examined the effects of MICA alleles on the course of the disease and development of /"amyloidosis"/ in the M694V homozygous patients, A5 allele had a protective effect against the development of /"amyloidosis"/ (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the /"MEFV"/ genotypes seem clear, there are definitely other modifying factors or genes on the development of /"amyloidosis"/ and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in /"FMF"/. | [
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17102945 | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF. | The contribution of genotypes at the /"MICA"/ gene triplet repeat polymorphisms and MEFV mutations to /"amyloidosis"/ and course of the disease in the patients with familial Mediterranean fever. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (/"MICA"/) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and /"amyloidosis"/ in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without /"amyloidosis"/, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. /"MICA"/ transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from /"MICA"/ locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and /"amyloidosis"/ were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of /"MICA"/ alleles as an independently risk factor on the /"amyloidosis"/ development. However, when we examined the effects of /"MICA"/ alleles on the course of the disease and development of /"amyloidosis"/ in the M694V homozygous patients, A5 allele had a protective effect against the development of /"amyloidosis"/ (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of /"amyloidosis"/ and on the course of the disease. For example, some /"MICA"/ alleles have a protective effect on the prognostic factors in FMF. | [
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17102945 | The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF. | The contribution of genotypes at the /"MICA"/ gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with /"familial Mediterranean fever"/. | OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (/"MICA"/) triplet repeat polymorphism on the severity and clinical features of /"familial Mediterranean fever"/ (/"FMF"/) and amyloidosis in a group of Turkish /"FMF"/ patients. METHODS: We evaluated 105 adult /"FMF"/ patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of /"FMF"/ or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. /"MICA"/ transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from /"MICA"/ locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of /"MICA"/ alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of /"MICA"/ alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some /"MICA"/ alleles have a protective effect on the prognostic factors in /"FMF"/. | [
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} | No |
17116328 | Placental abruption is more frequent in women with the angiotensinogen Thr235 mutation. | OBJECTIVE: Obstetrical complications such as preeclampsia, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the angiotensinogen (AGT) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the AGT Thr235 mutation increases the risk of placental abruption. MATERIALS AND METHODS: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. AGT Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: AGT genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of AGT genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). AGT mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The AGT Thr235 mutation was observed more frequently in placental abruption. AGT Thr235 mutation may be considered a risk factor for placental abruption. | /"Placental abruption"/ is more frequent in women with the /"angiotensinogen"/ Thr235 mutation. | OBJECTIVE: Obstetrical complications such as preeclampsia, fetal growth restriction, and /"placental abruption"/ are associated with inadequate placental perfusion. Previous studies have shown that the /"angiotensinogen"/ (/"AGT"/) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the /"AGT"/ Thr235 mutation increases the risk of /"placental abruption"/. MATERIALS AND METHODS: We compared 62 placentas from women who had /"placental abruption"/ with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. /"AGT"/ Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: /"AGT"/ genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of /"AGT"/ genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). /"AGT"/ mutant allele frequency in /"placental abruption"/ (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The /"AGT"/ Thr235 mutation was observed more frequently in /"placental abruption"/. /"AGT"/ Thr235 mutation may be considered a risk factor for /"placental abruption"/. | [
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} | Yes |
17116328 | Placental abruption is more frequent in women with the angiotensinogen Thr235 mutation. | OBJECTIVE: Obstetrical complications such as preeclampsia, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the angiotensinogen (AGT) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the AGT Thr235 mutation increases the risk of placental abruption. MATERIALS AND METHODS: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. AGT Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: AGT genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of AGT genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). AGT mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The AGT Thr235 mutation was observed more frequently in placental abruption. AGT Thr235 mutation may be considered a risk factor for placental abruption. | Placental abruption is more frequent in women with the /"angiotensinogen"/ Thr235 mutation. | OBJECTIVE: Obstetrical complications such as /"preeclampsia"/, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the /"angiotensinogen"/ (/"AGT"/) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in /"preeclampsia"/. This study was done to evaluate whether the /"AGT"/ Thr235 mutation increases the risk of placental abruption. MATERIALS AND METHODS: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. /"AGT"/ Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: /"AGT"/ genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of /"AGT"/ genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). /"AGT"/ mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The /"AGT"/ Thr235 mutation was observed more frequently in placental abruption. /"AGT"/ Thr235 mutation may be considered a risk factor for placental abruption. | [
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17121882 | Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression. CONCLUSIONS: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | /"Reprimo"/ methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: /"Reprimo"/, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of /"esophageal cancer"/. Our aim was to determine whether and at what phase of neoplastic progression /"Reprimo"/ methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether /"Reprimo"/ expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for /"Reprimo"/ was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on /"esophageal carcinoma"/ cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of /"Reprimo"/ methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). /"Reprimo"/ methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of /"Reprimo"/ methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced /"Reprimo"/ methylation and increased /"Reprimo"/ expression. CONCLUSIONS: /"Reprimo"/ methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | [
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17121882 | Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression. CONCLUSIONS: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | /"Reprimo"/ methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: /"Reprimo"/, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression /"Reprimo"/ methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether /"Reprimo"/ expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for /"Reprimo"/ was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In /"Barrett's esophagus"/ (/"BE"/; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of /"Reprimo"/ methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between /"BE"/ and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). /"Reprimo"/ methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 /"BE"/, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of /"Reprimo"/ methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced /"Reprimo"/ methylation and increased /"Reprimo"/ expression. CONCLUSIONS: /"Reprimo"/ methylation occurs significantly more frequently in /"BE"/, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | [
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} | Yes |
17121882 | Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression. CONCLUSIONS: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | /"Reprimo"/ methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: /"Reprimo"/, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression /"Reprimo"/ methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether /"Reprimo"/ expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for /"Reprimo"/ was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and /"esophageal adenocarcinoma"/ (/"EAC"/; P=0.00003), the level and frequency of /"Reprimo"/ methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and /"EAC"/, HGD and /"EAC"/, or NE and esophageal squamous cell carcinoma (ESCC). /"Reprimo"/ methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 /"EAC"/. Analysis of /"Reprimo"/ methylation in /"EAC"/ versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 /"EAC"/ cells reduced /"Reprimo"/ methylation and increased /"Reprimo"/ expression. CONCLUSIONS: /"Reprimo"/ methylation occurs significantly more frequently in BE, HGD, and /"EAC"/ than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | [
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} | No |
17121882 | Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression. CONCLUSIONS: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | /"Reprimo"/ methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. | PURPOSE: /"Reprimo"/, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression /"Reprimo"/ methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether /"Reprimo"/ expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for /"Reprimo"/ was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. RESULTS: In Barrett's esophagus (BE; P=0.001), high-grade dysplasia (HGD; P=0.001), and esophageal adenocarcinoma (EAC; P=0.00003), the level and frequency of /"Reprimo"/ methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and /"esophageal squamous cell carcinoma"/ (/"ESCC"/). /"Reprimo"/ methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 /"ESCC"/, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of /"Reprimo"/ methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P<0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced /"Reprimo"/ methylation and increased /"Reprimo"/ expression. CONCLUSIONS: /"Reprimo"/ methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or /"ESCC"/, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia. | [
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17131847 | [The hemostasis parameters and ACE gene polymorphism in patients with essential hypertension treated with perindopril]. | PURPOSE: 1. The assessment in haemostasis system, fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor type-1, von Willebrand factor and beta-thromboglobulin (beta-TG) levels and the changes in renin-angiotensin system (RAS), by determined angiotensin converting enzyme I (ACE) activity, in patients with essential hypertension (in relation to left ventricular hypertrophy) in comparison with normotension subjects. 2. The analysis of changes in haemostasis and RAS during treatment with perindopril in relation to left ventricular hypertrophy (group LVH+ and LVH-). 3. The assessment of haemostasis parameters levels and ACE activity in effect of treatment with perindopril in relation to ACE gene I/D polymorphism. MATERIAL AND METHODS: The study involved 78 male divided on two groups: cases and controls. The cases contained 44 male outpatients (25-38 years old) with untreated essential hypertension without clinical feature of coronary heart disease and 34 age- and gender- matched healthy controls. CONCLUSION: 1. Untreated essential hypertension predisposes to the procoagulant state characterised by increased Fb level and suppressed of fibrinolysis. These changes not depend on ACE gene I/D polymorphism. The left ventricular hypertrophy not intensificates the procoagulant state. 2. The treatment with perindopril decreases blood pressure effectively independent of ACE gene I/D genotype and left ventricular hypertrophy. Perindopril impairs RAS activity, most in patients with ACE gene II genotype. The treatment with perindopril is only partially effective in alleviating the procoagulant state, by reducing fibrinogen level in II homozygotes due to its more potent inhibitory action on the RAS in this group. The treatment makes fibrinolysis better mainly to high t-PA levels, independently of ACE gene I/D polymorphism. 3. Left ventricular hypertrophy not differentiates the response on treatment in relation to haemostasis parameters and RAS, however there was a slight decrease in ACE activity in patients with left ventricular hypertrophy. 4. The changes in haemostasis system and ACE activity, observed during treatment, suggest the appearance of positive relation between haemostasis and RAS. Probably the antithrombotic act of perindopril is more pronounced in II genotype group. | [The hemostasis parameters and /"ACE"/ gene polymorphism in patients with essential /"hypertension"/ treated with perindopril]. | PURPOSE: 1. The assessment in haemostasis system, fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor type-1, von Willebrand factor and beta-thromboglobulin (beta-TG) levels and the changes in renin-angiotensin system (RAS), by determined /"angiotensin converting enzyme I"/ (/"ACE"/) activity, in patients with essential /"hypertension"/ (in relation to left ventricular hypertrophy) in comparison with normotension subjects. 2. The analysis of changes in haemostasis and RAS during treatment with perindopril in relation to left ventricular hypertrophy (group LVH+ and LVH-). 3. The assessment of haemostasis parameters levels and /"ACE"/ activity in effect of treatment with perindopril in relation to /"ACE"/ gene I/D polymorphism. MATERIAL AND METHODS: The study involved 78 male divided on two groups: cases and controls. The cases contained 44 male outpatients (25-38 years old) with untreated essential /"hypertension"/ without clinical feature of coronary heart disease and 34 age- and gender- matched healthy controls. CONCLUSION: 1. Untreated essential /"hypertension"/ predisposes to the procoagulant state characterised by increased Fb level and suppressed of fibrinolysis. These changes not depend on /"ACE"/ gene I/D polymorphism. The left ventricular hypertrophy not intensificates the procoagulant state. 2. The treatment with perindopril decreases blood pressure effectively independent of /"ACE"/ gene I/D genotype and left ventricular hypertrophy. Perindopril impairs RAS activity, most in patients with /"ACE"/ gene II genotype. The treatment with perindopril is only partially effective in alleviating the procoagulant state, by reducing fibrinogen level in II homozygotes due to its more potent inhibitory action on the RAS in this group. The treatment makes fibrinolysis better mainly to high t-PA levels, independently of /"ACE"/ gene I/D polymorphism. 3. Left ventricular hypertrophy not differentiates the response on treatment in relation to haemostasis parameters and RAS, however there was a slight decrease in /"ACE"/ activity in patients with left ventricular hypertrophy. 4. The changes in haemostasis system and /"ACE"/ activity, observed during treatment, suggest the appearance of positive relation between haemostasis and RAS. Probably the antithrombotic act of perindopril is more pronounced in II genotype group. | [
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17131847 | [The hemostasis parameters and ACE gene polymorphism in patients with essential hypertension treated with perindopril]. | PURPOSE: 1. The assessment in haemostasis system, fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor type-1, von Willebrand factor and beta-thromboglobulin (beta-TG) levels and the changes in renin-angiotensin system (RAS), by determined angiotensin converting enzyme I (ACE) activity, in patients with essential hypertension (in relation to left ventricular hypertrophy) in comparison with normotension subjects. 2. The analysis of changes in haemostasis and RAS during treatment with perindopril in relation to left ventricular hypertrophy (group LVH+ and LVH-). 3. The assessment of haemostasis parameters levels and ACE activity in effect of treatment with perindopril in relation to ACE gene I/D polymorphism. MATERIAL AND METHODS: The study involved 78 male divided on two groups: cases and controls. The cases contained 44 male outpatients (25-38 years old) with untreated essential hypertension without clinical feature of coronary heart disease and 34 age- and gender- matched healthy controls. CONCLUSION: 1. Untreated essential hypertension predisposes to the procoagulant state characterised by increased Fb level and suppressed of fibrinolysis. These changes not depend on ACE gene I/D polymorphism. The left ventricular hypertrophy not intensificates the procoagulant state. 2. The treatment with perindopril decreases blood pressure effectively independent of ACE gene I/D genotype and left ventricular hypertrophy. Perindopril impairs RAS activity, most in patients with ACE gene II genotype. The treatment with perindopril is only partially effective in alleviating the procoagulant state, by reducing fibrinogen level in II homozygotes due to its more potent inhibitory action on the RAS in this group. The treatment makes fibrinolysis better mainly to high t-PA levels, independently of ACE gene I/D polymorphism. 3. Left ventricular hypertrophy not differentiates the response on treatment in relation to haemostasis parameters and RAS, however there was a slight decrease in ACE activity in patients with left ventricular hypertrophy. 4. The changes in haemostasis system and ACE activity, observed during treatment, suggest the appearance of positive relation between haemostasis and RAS. Probably the antithrombotic act of perindopril is more pronounced in II genotype group. | [The hemostasis parameters and ACE gene polymorphism in patients with essential /"hypertension"/ treated with perindopril]. | PURPOSE: 1. The assessment in haemostasis system, fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor type-1, von Willebrand factor and /"beta-thromboglobulin"/ (/"beta-TG"/) levels and the changes in renin-angiotensin system (RAS), by determined angiotensin converting enzyme I (ACE) activity, in patients with essential /"hypertension"/ (in relation to left ventricular hypertrophy) in comparison with normotension subjects. 2. The analysis of changes in haemostasis and RAS during treatment with perindopril in relation to left ventricular hypertrophy (group LVH+ and LVH-). 3. The assessment of haemostasis parameters levels and ACE activity in effect of treatment with perindopril in relation to ACE gene I/D polymorphism. MATERIAL AND METHODS: The study involved 78 male divided on two groups: cases and controls. The cases contained 44 male outpatients (25-38 years old) with untreated essential /"hypertension"/ without clinical feature of coronary heart disease and 34 age- and gender- matched healthy controls. CONCLUSION: 1. Untreated essential /"hypertension"/ predisposes to the procoagulant state characterised by increased Fb level and suppressed of fibrinolysis. These changes not depend on ACE gene I/D polymorphism. The left ventricular hypertrophy not intensificates the procoagulant state. 2. The treatment with perindopril decreases blood pressure effectively independent of ACE gene I/D genotype and left ventricular hypertrophy. Perindopril impairs RAS activity, most in patients with ACE gene II genotype. The treatment with perindopril is only partially effective in alleviating the procoagulant state, by reducing fibrinogen level in II homozygotes due to its more potent inhibitory action on the RAS in this group. The treatment makes fibrinolysis better mainly to high t-PA levels, independently of ACE gene I/D polymorphism. 3. Left ventricular hypertrophy not differentiates the response on treatment in relation to haemostasis parameters and RAS, however there was a slight decrease in ACE activity in patients with left ventricular hypertrophy. 4. The changes in haemostasis system and ACE activity, observed during treatment, suggest the appearance of positive relation between haemostasis and RAS. Probably the antithrombotic act of perindopril is more pronounced in II genotype group. | [
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17135225 | The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population. | OBJECTIVES: A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set. | The 620W allele is the /"PTPN22"/ genetic variant conferring susceptibility to /"RA"/ in a Dutch population. | OBJECTIVES: A missense SNP, C1858T, in /"PTPN22"/ has been identified as a genetic risk factor for /"rheumatoid arthritis"/ (/"RA"/). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with /"RA"/ in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 /"RA"/ patients and 286 controls were genotyped for 13 /"PTPN22"/ single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 /"RA"/ and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with /"RA"/ in our Dutch population carries the /"PTPN22"/ 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' /"PTPN22"/ SNP, rs3789604, with /"RA"/ susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole /"PTPN22"/ variant predisposing to /"RA"/ in our white Dutch sample set. | [
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"entity_id": "D001172",
"entity_type": "Disease",
"text_name": "rheumatoid arthritis"
} | Yes |
17135225 | The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population. | OBJECTIVES: A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set. | The 620W allele is the /"PTPN22"/ genetic variant conferring susceptibility to RA in a Dutch population. | OBJECTIVES: A missense SNP, C1858T, in /"PTPN22"/ has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 RA patients and 286 controls were genotyped for 13 /"PTPN22"/ single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the /"Leiden early arthritis"/ inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with RA in our Dutch population carries the /"PTPN22"/ 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' /"PTPN22"/ SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole /"PTPN22"/ variant predisposing to RA in our white Dutch sample set. | [
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} | No |
17138064 | The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation. | Cytomegalovirus (CMV) seronegative recipients of kidneys from CMV seropositive donors are at a high risk of CMV infection after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of infection. Effects of IL10, IL6 and IFNG gene polymorphisms, known to affect CMV infectivity, were investigated in 71 CMV seronegative recipients of grafts from CMV seropositive cadaver donors. Donor IL10(-1082 AA) genotype reduced the incidence of CMV infection (p=0.031) and CMV episodes in these patients tended to occur later (AA: median 83 days, AG/GG: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor IL10(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of CMV infection. We conclude that donor IL10 gene polymorphisms may influence the likelihood of CMV infection in the high risk patients investigated. | The impact of donor cytokine gene polymorphisms on the incidence of /"cytomegalovirus infection"/ after kidney transplantation. | /"Cytomegalovirus"/ (/"CMV"/) seronegative recipients of kidneys from /"CMV"/ seropositive donors are at a high risk of /"CMV infection"/ after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of infection. Effects of /"IL10"/, IL6 and IFNG gene polymorphisms, known to affect /"CMV infectivity"/, were investigated in 71 /"CMV"/ seronegative recipients of grafts from /"CMV"/ seropositive cadaver donors. Donor /"IL10"/(-1082 AA) genotype reduced the incidence of /"CMV infection"/ (p=0.031) and /"CMV"/ episodes in these patients tended to occur later (AA: median 83 days, AG/GG: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor /"IL10"/(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of /"CMV infection"/. We conclude that donor /"IL10"/ gene polymorphisms may influence the likelihood of /"CMV infection"/ in the high risk patients investigated. | [
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17138064 | The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation. | Cytomegalovirus (CMV) seronegative recipients of kidneys from CMV seropositive donors are at a high risk of CMV infection after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of infection. Effects of IL10, IL6 and IFNG gene polymorphisms, known to affect CMV infectivity, were investigated in 71 CMV seronegative recipients of grafts from CMV seropositive cadaver donors. Donor IL10(-1082 AA) genotype reduced the incidence of CMV infection (p=0.031) and CMV episodes in these patients tended to occur later (AA: median 83 days, AG/GG: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor IL10(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of CMV infection. We conclude that donor IL10 gene polymorphisms may influence the likelihood of CMV infection in the high risk patients investigated. | The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation. | Cytomegalovirus (CMV) seronegative recipients of kidneys from CMV seropositive donors are at a high risk of CMV infection after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of /"infection"/. Effects of /"IL10"/, IL6 and IFNG gene polymorphisms, known to affect CMV infectivity, were investigated in 71 CMV seronegative recipients of grafts from CMV seropositive cadaver donors. Donor /"IL10"/(-1082 AA) genotype reduced the incidence of CMV infection (p=0.031) and CMV episodes in these patients tended to occur later (AA: median 83 days, AG/GG: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor /"IL10"/(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of CMV infection. We conclude that donor /"IL10"/ gene polymorphisms may influence the likelihood of CMV infection in the high risk patients investigated. | [
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17151092 | Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. | As inflammation emerges as a risk factor for prostate cancer (PCa), there is potential for chemoprevention by anti-inflammatory agents. Dietary phytochemicals have been shown to have chemopreventive properties which may include anti-inflammatory activities. In this study, we demonstrate a role for mitogen-activated protein kinase phosphatase-5 (MKP5) in mediating anti-inflammatory activities of the phytochemicals curcumin, resveratrol and [6]-gingerol. We utilized the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta to increase p38-dependent nuclear factor kappa-B (NFkappaB) activation and expression of pro-inflammatory genes cyclooxygenase-2 (COX-2), IL-6 and IL-8 in normal prostatic epithelial cells. MKP5 over-expression decreased cytokine-induced NFkappaB activation, COX-2, IL-6 and IL-8 in normal prostatic epithelial cells, suggesting potent anti-inflammatory activity of MKP5. Pretreatment of cells with a p38 inhibitor mimicked the results observed with MKP5 over-expression, further implicating p38 inhibition as the main activity of MKP5. Curcumin, the phytochemical found in turmeric, up-regulated MKP5, subsequently decreasing cytokine-induced p38-dependent pro-inflammatory changes in normal prostatic epithelial cells. Resveratrol and [6]-gingerol, phytochemicals present in red wine and ginger, respectively, also up-regulated MKP5 in normal prostate epithelial cells. Moreover, we found that PCa cell lines DU 145, PC-3, LNCaP and LAPC-4 retained the ability to up-regulate MKP5 following curcumin, resveratrol and [6]-gingerol exposure, suggesting utility of these phytochemicals in PCa treatment. In summary, our findings show direct anti-inflammatory activity of MKP5 in prostate cells and suggest that up-regulation of MKP5 by phytochemicals may contribute to their chemopreventive actions by decreasing prostatic inflammation. | Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by /"MAP kinase phosphatase-5"/ in prostate cells. | As /"inflammation"/ emerges as a risk factor for prostate cancer (PCa), there is potential for chemoprevention by anti-inflammatory agents. Dietary phytochemicals have been shown to have chemopreventive properties which may include anti-inflammatory activities. In this study, we demonstrate a role for /"mitogen-activated protein kinase phosphatase-5"/ (/"MKP5"/) in mediating anti-inflammatory activities of the phytochemicals curcumin, resveratrol and [6]-gingerol. We utilized the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta to increase p38-dependent nuclear factor kappa-B (NFkappaB) activation and expression of pro-inflammatory genes cyclooxygenase-2 (COX-2), IL-6 and IL-8 in normal prostatic epithelial cells. /"MKP5"/ over-expression decreased cytokine-induced NFkappaB activation, COX-2, IL-6 and IL-8 in normal prostatic epithelial cells, suggesting potent anti-inflammatory activity of /"MKP5"/. Pretreatment of cells with a p38 inhibitor mimicked the results observed with /"MKP5"/ over-expression, further implicating p38 inhibition as the main activity of /"MKP5"/. Curcumin, the phytochemical found in turmeric, up-regulated /"MKP5"/, subsequently decreasing cytokine-induced p38-dependent pro-inflammatory changes in normal prostatic epithelial cells. Resveratrol and [6]-gingerol, phytochemicals present in red wine and ginger, respectively, also up-regulated /"MKP5"/ in normal prostate epithelial cells. Moreover, we found that PCa cell lines DU 145, PC-3, LNCaP and LAPC-4 retained the ability to up-regulate /"MKP5"/ following curcumin, resveratrol and [6]-gingerol exposure, suggesting utility of these phytochemicals in PCa treatment. In summary, our findings show direct anti-inflammatory activity of /"MKP5"/ in prostate cells and suggest that up-regulation of /"MKP5"/ by phytochemicals may contribute to their chemopreventive actions by decreasing prostatic inflammation. | [
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