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11303592 | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. | This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations. | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to /"breast cancer"/. | This study was undertaken to examine if /"glutathione S-transferase"/ (GST) M1, M3, P1, and T1 genotypes affected /"breast cancer"/ risk in Finnish women. The study population consisted of 483 incident /"breast cancer"/ cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for /"breast cancer"/. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal /"breast cancer"/ risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of /"breast cancer"/ was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of /"breast cancer"/ was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual /"breast cancer"/ risk, especially in certain combinations. | [
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11303592 | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. | This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations. | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to /"breast cancer"/. | This study was undertaken to examine if /"glutathione S-transferase"/ (GST) M1, M3, P1, and T1 genotypes affected /"breast cancer"/ risk in Finnish women. The study population consisted of 483 incident /"breast cancer"/ cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for /"breast cancer"/. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal /"breast cancer"/ risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of /"breast cancer"/ was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of /"breast cancer"/ was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual /"breast cancer"/ risk, especially in certain combinations. | [
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11303592 | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. | This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations. | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to /"breast cancer"/. | This study was undertaken to examine if /"glutathione S-transferase"/ (GST) M1, M3, P1, and T1 genotypes affected /"breast cancer"/ risk in Finnish women. The study population consisted of 483 incident /"breast cancer"/ cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for /"breast cancer"/. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal /"breast cancer"/ risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of /"breast cancer"/ was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of /"breast cancer"/ was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual /"breast cancer"/ risk, especially in certain combinations. | [
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11303592 | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. | This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations. | Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to /"breast cancer"/. | This study was undertaken to examine if /"glutathione S-transferase"/ (GST) M1, M3, P1, and T1 genotypes affected /"breast cancer"/ risk in Finnish women. The study population consisted of 483 incident /"breast cancer"/ cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for /"breast cancer"/. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal /"breast cancer"/ risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of /"breast cancer"/ was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of /"breast cancer"/ was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual /"breast cancer"/ risk, especially in certain combinations. | [
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11313768 | Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. | Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA. | Organization of the /"mevalonate kinase"/ (/"MVK"/) gene and identification of novel mutations causing /"mevalonic aciduria"/ and hyperimmunoglobulinaemia D and periodic fever syndrome. | /"Mevalonic aciduria"/ (/"MA"/) and hyperimmunoglobulinaemia D and periodic fever syndrome (/"HIDS"/) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme /"mevalonate kinase"/ (/"MK"/) resulting from mutations in the encoding /"MVK"/ gene. Thus far, disease-causing mutations only could be detected by analysis of /"MVK"/ cDNA. We now describe the genomic organization of the human /"MVK"/ gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 /"HIDS"/ and /"MA"/ patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between /"HIDS"/ and /"MA"/. | [
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11313768 | Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. | Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA. | Organization of the /"mevalonate kinase"/ (/"MVK"/) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and /"periodic fever syndrome"/. | Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and /"periodic fever syndrome"/ (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme /"mevalonate kinase"/ (/"MK"/) resulting from mutations in the encoding /"MVK"/ gene. Thus far, disease-causing mutations only could be detected by analysis of /"MVK"/ cDNA. We now describe the genomic organization of the human /"MVK"/ gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA. | [
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11323423 | Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation. | Human mutations in the transcription factor SOX9 cause campomelic dysplasia/autosomal sex reversal. Here we identify and characterize two novel heterozygous mutations, F154L and A158T, that substitute conserved "hydrophobic core" amino acids of the high mobility group domain at positions thought to stabilize SOX9 conformation. Circular dichroism studies indicated that both mutations disrupt alpha-helicity within their high mobility group domain, whereas tertiary structure is essentially maintained as judged by fluorescence spectroscopy. In cultured cells, strictly nuclear localization was observed for wild type SOX9 and the F154L mutant; however, the A158T mutant showed a 2-fold reduction in nuclear import efficiency. Importin-beta was demonstrated to be the nuclear transport receptor recognized by SOX9, with both mutant proteins binding importin-beta with wild type affinity. Whereas DNA bending was unaffected, DNA binding was drastically reduced in both mutants (to 5% of wild type activity in F154L, 17% in A158T). Despite this large effect, transcriptional activation in cultured cells was only reduced to 26% in F154L and 62% in A158T of wild type activity, suggesting that a small loss of SOX9 transactivation activity could be sufficient to disrupt proper regulation of target genes during bone and testis formation. Thus, clinically relevant mutations of SOX9 affect protein structure leading to compound effects of reduced nuclear import and reduced DNA binding, the net effect being loss of transcriptional activation. | Compound effects of point mutations causing /"campomelic dysplasia"//autosomal sex reversal upon /"SOX9"/ structure, nuclear transport, DNA binding, and transcriptional activation. | Human mutations in the transcription factor /"SOX9"/ cause /"campomelic dysplasia"//autosomal sex reversal. Here we identify and characterize two novel heterozygous mutations, F154L and A158T, that substitute conserved "hydrophobic core" amino acids of the high mobility group domain at positions thought to stabilize /"SOX9"/ conformation. Circular dichroism studies indicated that both mutations disrupt alpha-helicity within their high mobility group domain, whereas tertiary structure is essentially maintained as judged by fluorescence spectroscopy. In cultured cells, strictly nuclear localization was observed for wild type /"SOX9"/ and the F154L mutant; however, the A158T mutant showed a 2-fold reduction in nuclear import efficiency. Importin-beta was demonstrated to be the nuclear transport receptor recognized by /"SOX9"/, with both mutant proteins binding importin-beta with wild type affinity. Whereas DNA bending was unaffected, DNA binding was drastically reduced in both mutants (to 5% of wild type activity in F154L, 17% in A158T). Despite this large effect, transcriptional activation in cultured cells was only reduced to 26% in F154L and 62% in A158T of wild type activity, suggesting that a small loss of /"SOX9"/ transactivation activity could be sufficient to disrupt proper regulation of target genes during bone and testis formation. Thus, clinically relevant mutations of /"SOX9"/ affect protein structure leading to compound effects of reduced nuclear import and reduced DNA binding, the net effect being loss of transcriptional activation. | [
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} | Yes |
11331106 | Study of polymorphisms in the CYP2E1 gene in patients with alcoholic pancreatitis. | Cytochrome P450IIEI (CYP2E1) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the CYP2E1 gene have been identified. A polymorphism at position -35 [G(-35)T] appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the CYP2E1 gene are associated with alcoholic pancreatitis. DNA was extracted from peripheral blood of 38 patients with alcoholic chronic pancreatitis (CP), 19 patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the CP, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the CYP2E1 gene are unlikely to be involved in the susceptibility and pathogenesis of alcoholic pancreatitis. | Study of polymorphisms in the /"CYP2E1"/ gene in patients with /"alcoholic pancreatitis"/. | Cytochrome P450IIEI (/"CYP2E1"/) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the /"CYP2E1"/ gene have been identified. A polymorphism at position -35 [G(-35)T] appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the /"CYP2E1"/ gene are associated with /"alcoholic pancreatitis"/. DNA was extracted from peripheral blood of 38 patients with /"alcoholic chronic pancreatitis"/ (CP), 19 patients with /"alcoholic acute pancreatitis"/ (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the CP, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the /"CYP2E1"/ gene are unlikely to be involved in the susceptibility and pathogenesis of /"alcoholic pancreatitis"/. | [
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} | Yes |
11331106 | Study of polymorphisms in the CYP2E1 gene in patients with alcoholic pancreatitis. | Cytochrome P450IIEI (CYP2E1) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the CYP2E1 gene have been identified. A polymorphism at position -35 [G(-35)T] appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the CYP2E1 gene are associated with alcoholic pancreatitis. DNA was extracted from peripheral blood of 38 patients with alcoholic chronic pancreatitis (CP), 19 patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the CP, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the CYP2E1 gene are unlikely to be involved in the susceptibility and pathogenesis of alcoholic pancreatitis. | Study of polymorphisms in the /"CYP2E1"/ gene in patients with alcoholic pancreatitis. | Cytochrome P450IIEI (/"CYP2E1"/) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the /"CYP2E1"/ gene have been identified. A polymorphism at position -35 [G(-35)T] appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the /"CYP2E1"/ gene are associated with alcoholic pancreatitis. DNA was extracted from peripheral blood of 38 patients with alcoholic chronic pancreatitis (/"CP"/), 19 patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the /"CP"/, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the /"CYP2E1"/ gene are unlikely to be involved in the susceptibility and pathogenesis of alcoholic pancreatitis. | [
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"text_name": "CP"
} | No |
11340230 | Association of apolipoprotein E polymorphism with outcome after aneurysmal subarachnoid hemorrhage: a preliminary study. | BACKGROUND AND PURPOSE: Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. APOE genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of apolipoprotein E polymorphism with the outcome after aneurysmal SAH. METHODS: A total of 160 consecutive patients were admitted after SAH to a neurosurgical unit. The clinical assessment after the SAH was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: 126 patients had aneurysmatic SAH, and detailed information on outcome and APOE genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with APOE epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the APOE epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic association of APOE polymorphism with outcome after spontaneous aneurysmal SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH. | Association of /"apolipoprotein E"/ polymorphism with outcome after /"aneurysmal subarachnoid hemorrhage"/: a preliminary study. | BACKGROUND AND PURPOSE: Variation in the outcome after /"aneurysmal subarachnoid hemorrhage"/ (/"SAH"/) is not fully explained by known prognostic factors. /"APOE"/ genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of /"apolipoprotein E"/ polymorphism with the outcome after aneurysmal /"SAH"/. METHODS: A total of 160 consecutive patients were admitted after /"SAH"/ to a neurosurgical unit. The clinical assessment after the /"SAH"/ was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: /"APOE"/ genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: 126 patients had /"aneurysmatic SAH"/, and detailed information on outcome and /"APOE"/ genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with /"APOE"/ epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the /"APOE"/ epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic association of /"APOE"/ polymorphism with outcome after spontaneous aneurysmal /"SAH"/. Genetic factors thus seem to explain a part of individual differences in the recovery of /"SAH"/. | [
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11340230 | Association of apolipoprotein E polymorphism with outcome after aneurysmal subarachnoid hemorrhage: a preliminary study. | BACKGROUND AND PURPOSE: Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. APOE genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of apolipoprotein E polymorphism with the outcome after aneurysmal SAH. METHODS: A total of 160 consecutive patients were admitted after SAH to a neurosurgical unit. The clinical assessment after the SAH was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: 126 patients had aneurysmatic SAH, and detailed information on outcome and APOE genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with APOE epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the APOE epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic association of APOE polymorphism with outcome after spontaneous aneurysmal SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH. | Association of /"apolipoprotein E"/ polymorphism with outcome after aneurysmal subarachnoid hemorrhage: a preliminary study. | BACKGROUND AND PURPOSE: Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. /"APOE"/ genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of /"apolipoprotein E"/ polymorphism with the outcome after /"aneurysmal"/ SAH. METHODS: A total of 160 consecutive patients were admitted after SAH to a neurosurgical unit. The clinical assessment after the SAH was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: /"APOE"/ genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: 126 patients had aneurysmatic SAH, and detailed information on outcome and /"APOE"/ genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with /"APOE"/ epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the /"APOE"/ epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic association of /"APOE"/ polymorphism with outcome after spontaneous /"aneurysmal"/ SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH. | [
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11354633 | CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. | In order to investigate the incidence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with asthma, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the CFTR gene and its flanking intronic regions revealed that the proportion of CFTR mutations was 45% in asthma (P<0.05), 26.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in COPD patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant CFTR allele revealed the presence of CFTR function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six asthma patients, four DB patients (P<0.01), and two COPD patients (P<0.05). These results confirm the involvement of the CFTR gene in asthma, DB and possibly in COPD. | /"CFTR"/ gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with /"asthma"/, disseminated bronchiectasis and chronic obstructive pulmonary disease. | In order to investigate the incidence of /"cystic fibrosis transmembrane conductance regulator"/ (/"CFTR"/) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with /"asthma"/, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the /"CFTR"/ gene and its flanking intronic regions revealed that the proportion of /"CFTR"/ mutations was 45% in /"asthma"/ (P<0.05), 26.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three /"asthma"/ patients. The hyperactive M470 allele was found more frequently in COPD patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant /"CFTR"/ allele revealed the presence of /"CFTR"/ function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six /"asthma"/ patients, four DB patients (P<0.01), and two COPD patients (P<0.05). These results confirm the involvement of the /"CFTR"/ gene in /"asthma"/, DB and possibly in COPD. | [
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11354633 | CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. | In order to investigate the incidence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with asthma, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the CFTR gene and its flanking intronic regions revealed that the proportion of CFTR mutations was 45% in asthma (P<0.05), 26.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in COPD patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant CFTR allele revealed the presence of CFTR function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six asthma patients, four DB patients (P<0.01), and two COPD patients (P<0.05). These results confirm the involvement of the CFTR gene in asthma, DB and possibly in COPD. | /"CFTR"/ gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and /"chronic obstructive pulmonary disease"/. | In order to investigate the incidence of /"cystic fibrosis transmembrane conductance regulator"/ (/"CFTR"/) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with asthma, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with /"chronic obstructive pulmonary disease"/ (/"COPD"/), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the /"CFTR"/ gene and its flanking intronic regions revealed that the proportion of /"CFTR"/ mutations was 45% in asthma (P<0.05), 26.3% in DB (P>0.05), 16.7% in /"COPD"/ (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in /"COPD"/ patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant /"CFTR"/ allele revealed the presence of /"CFTR"/ function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six asthma patients, four DB patients (P<0.01), and two /"COPD"/ patients (P<0.05). These results confirm the involvement of the /"CFTR"/ gene in asthma, DB and possibly in /"COPD"/. | [
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11357375 | [Polymorphism of catalase and glutathione peroxidase genes in macrovascular complications in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients. | [Polymorphism of /"catalase"/ and glutathione peroxidase genes in macrovascular complications in patients with /"non-insulin-dependent diabetes mellitus"/ and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of /"catalase"/ (/"CAT"/) and glutathione peroxidase (GPX1), respectively, were studied in patients with /"non-insulin-dependent diabetes mellitus"/ (/"NIDDM"/) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive /"NIDDM"/ patients. | [
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11357375 | [Polymorphism of catalase and glutathione peroxidase genes in macrovascular complications in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients. | [Polymorphism of catalase and glutathione peroxidase genes in macrovascular complications in patients with /"non-insulin-dependent diabetes mellitus"/ and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (/"GPX1"/), respectively, were studied in patients with /"non-insulin-dependent diabetes mellitus"/ (/"NIDDM"/) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive /"NIDDM"/ patients. | [
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11357375 | [Polymorphism of catalase and glutathione peroxidase genes in macrovascular complications in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients. | [Polymorphism of /"catalase"/ and glutathione peroxidase genes in macrovascular complications in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of /"catalase"/ (/"CAT"/) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or /"stroke"/ (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or /"stroke"/ in hypertensive NIDDM patients. | [
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11357375 | [Polymorphism of catalase and glutathione peroxidase genes in macrovascular complications in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients. | [Polymorphism of catalase and glutathione peroxidase genes in /"macrovascular complications"/ in patients with non-insulin-dependent diabetes mellitus and hypertension]. | Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (/"GPX1"/), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients. | [
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11397889 | Linkage of the human inducible nitric oxide synthase gene to type 1 diabetes. | Exposure of human pancreatic islets to a mixture of cytokines induces expression of the inducible nitric oxide synthase (iNOS), impairs beta-cell function, and induces apoptosis. We performed a mutational scanning of all 27 exons of the human NOS2 gene and linkage transmission disequilibrium testing of identified NOS2 polymorphisms in a Danish nationwide type 1 diabetes mellitus (IDDM) family collection. Mutational screening was performed using PCR-amplified exons, followed by single stranded conformation polymorphism and verification of potential polymorphisms by sequencing. The transmission disequilibrium test was performed in an IDDM family material comprising 257 Danish families; 154 families were affected sibling pair families, and 103 families were simplex families. In total, 10 polymorphisms were identified in 8 exons, of which 4 were tested in the family material. A C/T single nucleotide polymorphism in exon 16 resulting in an amino acid substitution, Ser(608)Leu, showed linkage to IDDM in human leukocyte antigen DR3/4-positive affected offspring (P = 0.008; corrected P = 0.024). No other distorted transmission patterns were found for any other tested single nucleotide polymorphism or constructed haplotypes with the exception of those including data from exon 16. In conclusion, linkage of the human NOS2 gene to IDDM in a subset of patients supports a pathogenic role of nitric oxide in human IDDM. | Linkage of the human /"inducible nitric oxide synthase"/ gene to type 1 diabetes. | Exposure of human pancreatic islets to a mixture of cytokines induces expression of the /"inducible nitric oxide synthase"/ (/"iNOS"/), impairs beta-cell function, and induces apoptosis. We performed a mutational scanning of all 27 exons of the human /"NOS2"/ gene and linkage transmission disequilibrium testing of identified /"NOS2"/ polymorphisms in a Danish nationwide type 1 diabetes mellitus (/"IDDM"/) family collection. Mutational screening was performed using PCR-amplified exons, followed by single stranded conformation polymorphism and verification of potential polymorphisms by sequencing. The transmission disequilibrium test was performed in an /"IDDM"/ family material comprising 257 Danish families; 154 families were affected sibling pair families, and 103 families were simplex families. In total, 10 polymorphisms were identified in 8 exons, of which 4 were tested in the family material. A C/T single nucleotide polymorphism in exon 16 resulting in an amino acid substitution, Ser(608)Leu, showed linkage to /"IDDM"/ in human leukocyte antigen DR3/4-positive affected offspring (P = 0.008; corrected P = 0.024). No other distorted transmission patterns were found for any other tested single nucleotide polymorphism or constructed haplotypes with the exception of those including data from exon 16. In conclusion, linkage of the human /"NOS2"/ gene to /"IDDM"/ in a subset of patients supports a pathogenic role of nitric oxide in human /"IDDM"/. | [
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11397889 | Linkage of the human inducible nitric oxide synthase gene to type 1 diabetes. | Exposure of human pancreatic islets to a mixture of cytokines induces expression of the inducible nitric oxide synthase (iNOS), impairs beta-cell function, and induces apoptosis. We performed a mutational scanning of all 27 exons of the human NOS2 gene and linkage transmission disequilibrium testing of identified NOS2 polymorphisms in a Danish nationwide type 1 diabetes mellitus (IDDM) family collection. Mutational screening was performed using PCR-amplified exons, followed by single stranded conformation polymorphism and verification of potential polymorphisms by sequencing. The transmission disequilibrium test was performed in an IDDM family material comprising 257 Danish families; 154 families were affected sibling pair families, and 103 families were simplex families. In total, 10 polymorphisms were identified in 8 exons, of which 4 were tested in the family material. A C/T single nucleotide polymorphism in exon 16 resulting in an amino acid substitution, Ser(608)Leu, showed linkage to IDDM in human leukocyte antigen DR3/4-positive affected offspring (P = 0.008; corrected P = 0.024). No other distorted transmission patterns were found for any other tested single nucleotide polymorphism or constructed haplotypes with the exception of those including data from exon 16. In conclusion, linkage of the human NOS2 gene to IDDM in a subset of patients supports a pathogenic role of nitric oxide in human IDDM. | Linkage of the human /"inducible nitric oxide synthase"/ gene to type 1 /"diabetes"/. | Exposure of human pancreatic islets to a mixture of cytokines induces expression of the /"inducible nitric oxide synthase"/ (/"iNOS"/), impairs beta-cell function, and induces apoptosis. We performed a mutational scanning of all 27 exons of the human /"NOS2"/ gene and linkage transmission disequilibrium testing of identified /"NOS2"/ polymorphisms in a Danish nationwide type 1 /"diabetes mellitus"/ (IDDM) family collection. Mutational screening was performed using PCR-amplified exons, followed by single stranded conformation polymorphism and verification of potential polymorphisms by sequencing. The transmission disequilibrium test was performed in an IDDM family material comprising 257 Danish families; 154 families were affected sibling pair families, and 103 families were simplex families. In total, 10 polymorphisms were identified in 8 exons, of which 4 were tested in the family material. A C/T single nucleotide polymorphism in exon 16 resulting in an amino acid substitution, Ser(608)Leu, showed linkage to IDDM in human leukocyte antigen DR3/4-positive affected offspring (P = 0.008; corrected P = 0.024). No other distorted transmission patterns were found for any other tested single nucleotide polymorphism or constructed haplotypes with the exception of those including data from exon 16. In conclusion, linkage of the human /"NOS2"/ gene to IDDM in a subset of patients supports a pathogenic role of nitric oxide in human IDDM. | [
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11401923 | Epstein-Barr Virus and HLA-DPB1-*0301 in young adult Hodgkin's disease: evidence for inherited susceptibility to Epstein-Barr Virus in cases that are EBV(+ve). | Cases of Hodgkin's disease (HD) may be distinguished by whether they do [EBV-positive ((+ve)) cases] or do not [EBV-negative ((-ve)) cases] have evidence of EBV DNA in the Reed-Sternberg cells. Only one study has attempted to distinguish epidemiological risk factors for EBV(+ve) and EBV(-ve) HD, and none have compared inherited susceptibility. The present study involves a population-based case series of HD, diagnosed in patients between 16-24 years of age in the United Kingdom (n = 118), of whom 87% were classified by EBV status (EBV(+ve), 19, EBV(-ve), 84). History of infectious illness, EBV antibody titers, and HLA-DPB1 type have been compared in EBV(+ve) and EBV(-ve) cases. Reported infectious mononucleosis was more frequent in EBV(+ve) cases (odds ratio (OR), 5.10; 95% confidence interval (CI), 1.12-24.4). EBV antibody titers to viral capsid antigen were significantly higher in EBV(+ve) cases (P for trend = 0.02). Higher proportions of EBV(+ve) (43%) than EBV(-ve) (31%) cases typed positive for HLA-DPB1*0301, but this was not statistically significant; the association of infectious mononucleosis with EBV(+ve) cases was stronger in this HLA subgroup (OR, 17.1; 95%CI, 1.06-1177) than in other cases (OR, 1.24; 95% CI, 0.02-15.4). Although these results are based on small numbers of HD cases, they provide suggestive evidence that the etiology of EBV(+ve) HD may involve inherited susceptibility to EBV. | Epstein-Barr Virus and /"HLA-DPB1"/-*0301 in young adult /"Hodgkin's disease"/: evidence for inherited susceptibility to Epstein-Barr Virus in cases that are EBV(+ve). | Cases of /"Hodgkin's disease"/ (/"HD"/) may be distinguished by whether they do [EBV-positive ((+ve)) cases] or do not [EBV-negative ((-ve)) cases] have evidence of EBV DNA in the Reed-Sternberg cells. Only one study has attempted to distinguish epidemiological risk factors for EBV(+ve) and EBV(-ve) /"HD"/, and none have compared inherited susceptibility. The present study involves a population-based case series of /"HD"/, diagnosed in patients between 16-24 years of age in the United Kingdom (n = 118), of whom 87% were classified by EBV status (EBV(+ve), 19, EBV(-ve), 84). History of infectious illness, EBV antibody titers, and /"HLA-DPB1"/ type have been compared in EBV(+ve) and EBV(-ve) cases. Reported infectious mononucleosis was more frequent in EBV(+ve) cases (odds ratio (OR), 5.10; 95% confidence interval (CI), 1.12-24.4). EBV antibody titers to viral capsid antigen were significantly higher in EBV(+ve) cases (P for trend = 0.02). Higher proportions of EBV(+ve) (43%) than EBV(-ve) (31%) cases typed positive for /"HLA-DPB1"/*0301, but this was not statistically significant; the association of infectious mononucleosis with EBV(+ve) cases was stronger in this HLA subgroup (OR, 17.1; 95%CI, 1.06-1177) than in other cases (OR, 1.24; 95% CI, 0.02-15.4). Although these results are based on small numbers of /"HD"/ cases, they provide suggestive evidence that the etiology of EBV(+ve) /"HD"/ may involve inherited susceptibility to EBV. | [
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} | Yes |
11401923 | Epstein-Barr Virus and HLA-DPB1-*0301 in young adult Hodgkin's disease: evidence for inherited susceptibility to Epstein-Barr Virus in cases that are EBV(+ve). | Cases of Hodgkin's disease (HD) may be distinguished by whether they do [EBV-positive ((+ve)) cases] or do not [EBV-negative ((-ve)) cases] have evidence of EBV DNA in the Reed-Sternberg cells. Only one study has attempted to distinguish epidemiological risk factors for EBV(+ve) and EBV(-ve) HD, and none have compared inherited susceptibility. The present study involves a population-based case series of HD, diagnosed in patients between 16-24 years of age in the United Kingdom (n = 118), of whom 87% were classified by EBV status (EBV(+ve), 19, EBV(-ve), 84). History of infectious illness, EBV antibody titers, and HLA-DPB1 type have been compared in EBV(+ve) and EBV(-ve) cases. Reported infectious mononucleosis was more frequent in EBV(+ve) cases (odds ratio (OR), 5.10; 95% confidence interval (CI), 1.12-24.4). EBV antibody titers to viral capsid antigen were significantly higher in EBV(+ve) cases (P for trend = 0.02). Higher proportions of EBV(+ve) (43%) than EBV(-ve) (31%) cases typed positive for HLA-DPB1*0301, but this was not statistically significant; the association of infectious mononucleosis with EBV(+ve) cases was stronger in this HLA subgroup (OR, 17.1; 95%CI, 1.06-1177) than in other cases (OR, 1.24; 95% CI, 0.02-15.4). Although these results are based on small numbers of HD cases, they provide suggestive evidence that the etiology of EBV(+ve) HD may involve inherited susceptibility to EBV. | Epstein-Barr Virus and /"HLA-DPB1"/-*0301 in young adult Hodgkin's disease: evidence for inherited susceptibility to Epstein-Barr Virus in cases that are EBV(+ve). | Cases of Hodgkin's disease (HD) may be distinguished by whether they do [EBV-positive ((+ve)) cases] or do not [EBV-negative ((-ve)) cases] have evidence of EBV DNA in the Reed-Sternberg cells. Only one study has attempted to distinguish epidemiological risk factors for EBV(+ve) and EBV(-ve) HD, and none have compared inherited susceptibility. The present study involves a population-based case series of HD, diagnosed in patients between 16-24 years of age in the United Kingdom (n = 118), of whom 87% were classified by EBV status (EBV(+ve), 19, EBV(-ve), 84). History of /"infectious illness"/, EBV antibody titers, and /"HLA-DPB1"/ type have been compared in EBV(+ve) and EBV(-ve) cases. Reported infectious mononucleosis was more frequent in EBV(+ve) cases (odds ratio (OR), 5.10; 95% confidence interval (CI), 1.12-24.4). EBV antibody titers to viral capsid antigen were significantly higher in EBV(+ve) cases (P for trend = 0.02). Higher proportions of EBV(+ve) (43%) than EBV(-ve) (31%) cases typed positive for /"HLA-DPB1"/*0301, but this was not statistically significant; the association of infectious mononucleosis with EBV(+ve) cases was stronger in this HLA subgroup (OR, 17.1; 95%CI, 1.06-1177) than in other cases (OR, 1.24; 95% CI, 0.02-15.4). Although these results are based on small numbers of HD cases, they provide suggestive evidence that the etiology of EBV(+ve) HD may involve inherited susceptibility to EBV. | [
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), /"NAT2"/, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, /"glutathione S-transferase M1"/ (/"GSTM1"/), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving /"N-acetyltransferase 1"/ (/"NAT1"/), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), /"CYP2D6"/, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, /"cytochrome P450 1A1"/ (/"CYP1A1"/), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, /"CYP2E1"/, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"end_idx": "50",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and /"apolipoprotein E"/ were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for /"colorectal cancer"/. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of /"colorectal cancer"/. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), /"GSTT1"/ and apolipoprotein E were compared in 219 white adults with sporadic /"colorectal cancer"/ and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with /"colorectal cancer"/. Inheritance of the /"GSTT1"/ null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and /"colorectal cancer"/ risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancer"
} | Yes |
11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), /"GSTT1"/ and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the /"GSTT1"/ null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "cancer"
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), /"GSTT1"/ and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the /"GSTT1"/ null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "cancers"
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), /"CYP2D6"/, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"entity_id": "D009369",
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"text_name": "cancers"
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), /"NAT2"/, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, /"glutathione S-transferase M1"/ (/"GSTM1"/), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), /"GSTT1"/ and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the /"GSTT1"/ null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to /"dietary or other environmental carcinogens"/. | [
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"entity_id": "2952",
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"entity_id": "D018876",
"entity_type": "Disease",
"text_name": "dietary or other environmental carcinogens"
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), /"GSTT1"/ and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the /"GSTT1"/ null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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11422615 | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | Metabolic genotypes and risk for colorectal cancer. | BACKGROUND: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. METHODS: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, /"glutathione S-transferase M1"/ (/"GSTM1"/), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of /"cancer"/ that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) /"cancers"/ in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33). CONCLUSION: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between /"cancer"/ risk, metabolic genotypes and exposure to dietary or other environmental carcinogens. | [
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"text_name": "cancer"
} | No |
11425413 | Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. | Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis. | Association between insertion mutation in /"NOD2"/ gene and Crohn's disease in German and British populations. | Background Genetic predisposition to /"inflammatory bowel disease"/ (/"IBD"/) has been shown by epidemiological and linkage studies. Genetic linkage of /"IBD"/ to chromosome 16 has been previously observed and replicated in independent populations. The recently identified /"NOD2"/ gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the /"NOD2"/ gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with /"IBD"/ from 309 German or British families, 369 German trios (ie, German patients with /"sporadic IBD"/ and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the /"NOD2"/ gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis. | [
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"entity_id": "64127",
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"entity_id": "64127",
"entity_type": "Gene",
"text_name": "NOD2"
} | {
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"entity_id": "D015212",
"entity_type": "Disease",
"text_name": "inflammatory bowel disease"
} | Yes |
11425413 | Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. | Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis. | Association between insertion mutation in /"NOD2"/ gene and /"Crohn's disease"/ in German and British populations. | Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified /"NOD2"/ gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the /"NOD2"/ gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with /"Crohn's disease"/ and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with /"Crohn's disease"/ (combined p<0.0001); the association was confirmed in the 304 German trios with /"Crohn's disease"/. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the /"NOD2"/ gene confers a substantially increased susceptibility to /"Crohn's disease"/ but not to ulcerative colitis. | [
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11425413 | Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. | Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis. | Association between insertion mutation in /"NOD2"/ gene and Crohn's disease in German and British populations. | Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified /"NOD2"/ gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the /"NOD2"/ gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and /"ulcerative colitis"/. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with /"ulcerative colitis"/. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the /"NOD2"/ gene confers a substantially increased susceptibility to Crohn's disease but not to /"ulcerative colitis"/. | [
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} | Yes |
11450852 | Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia. | Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous. | Two mutations of the /"Gsalpha"/ gene in two Japanese patients with /"sporadic pseudohypoparathyroidism type Ia"/. | /"Pseudohypoparathyroidism Ia"/ (/"PHP-Ia"/), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the /"Gsalpha"/ gene were identified in two Japanese patients with /"sporadic PHP-Ia"/. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of /"Gsalpha"/ protein, this mutation may impair Gs protein function. We report here one novel /"Gsalpha"/ mutation, and note that mutations in Japanese patients with /"PHP-Ia"/ are probably heterogeneous. | [
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11450852 | Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia. | Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous. | Two mutations of the /"Gsalpha"/ gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia. | Pseudohypoparathyroidism Ia (PHP-Ia), is an /"inherited disease"/ with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the /"Gsalpha"/ gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of /"Gsalpha"/ protein, this mutation may impair Gs protein function. We report here one novel /"Gsalpha"/ mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous. | [
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11462241 | Characterization of 11 novel mutations in the X-linked chronic granulomatous disease (CYBB gene). | The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the CYBB gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections. We investigated 16 unrelated male patients with suspected X-linked CGD and gp91-phox deficiency. A mutation was found in the CYBB gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R gp-91phox). One patient had an in-frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001. | Characterization of 11 novel mutations in the /"X-linked chronic granulomatous disease"/ (/"CYBB"/ gene). | The most frequent form of /"chronic granulomatous disease"/ (/"CGD"/) is caused by inactivation of the /"CYBB"/ gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections. We investigated 16 unrelated male patients with suspected /"X-linked CGD and gp91-phox deficiency"/. A mutation was found in the /"CYBB"/ gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R /"gp-91phox"/). One patient had an in-frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001. | [
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} | Yes |
11462241 | Characterization of 11 novel mutations in the X-linked chronic granulomatous disease (CYBB gene). | The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the CYBB gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections. We investigated 16 unrelated male patients with suspected X-linked CGD and gp91-phox deficiency. A mutation was found in the CYBB gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R gp-91phox). One patient had an in-frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001. | Characterization of 11 novel mutations in the X-linked chronic granulomatous disease (/"CYBB"/ gene). | The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the /"CYBB"/ gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating /"bacterial and fungal infections"/. We investigated 16 unrelated male patients with suspected X-linked CGD and gp91-phox deficiency. A mutation was found in the /"CYBB"/ gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R /"gp-91phox"/). One patient had an in-frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001. | [
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} | No |
11463752 | Microsatellite DNA polymorphism of human adrenomedullin gene in normotensive subjects and patients with essential hypertension. | Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human AM gene and have determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to hypertension. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57+/-5 years and 266 patients with essential hypertension (EH) age 53+/-11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117+/-13/73+/-9 mm Hg in NT and 170+/-23/104+/-12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH (chi(2)=9.43, P=0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT (chi(2)=7.62, P=0.007). In NT, plasma AM concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes. | Microsatellite DNA polymorphism of human /"adrenomedullin"/ gene in normotensive subjects and patients with essential /"hypertension"/. | /"Adrenomedullin"/ (/"AM"/) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human /"AM"/ gene and have determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in /"AM"/ gene and the predisposition to /"hypertension"/. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57+/-5 years and 266 patients with essential /"hypertension"/ (EH) age 53+/-11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117+/-13/73+/-9 mm Hg in NT and 170+/-23/104+/-12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH (chi(2)=9.43, P=0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT (chi(2)=7.62, P=0.007). In NT, plasma /"AM"/ concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of /"AM"/ gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes. | [
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} | Yes |
11463752 | Microsatellite DNA polymorphism of human adrenomedullin gene in normotensive subjects and patients with essential hypertension. | Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human AM gene and have determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to hypertension. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57+/-5 years and 266 patients with essential hypertension (EH) age 53+/-11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117+/-13/73+/-9 mm Hg in NT and 170+/-23/104+/-12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH (chi(2)=9.43, P=0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT (chi(2)=7.62, P=0.007). In NT, plasma AM concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes. | Microsatellite DNA polymorphism of human /"adrenomedullin"/ gene in normotensive subjects and patients with essential hypertension. | /"Adrenomedullin"/ (/"AM"/) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human /"AM"/ gene and have determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in /"AM"/ gene and the predisposition to hypertension. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57+/-5 years and 266 patients with essential hypertension (EH) age 53+/-11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117+/-13/73+/-9 mm Hg in NT and 170+/-23/104+/-12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different /"CA-repeat numbers"/: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH (chi(2)=9.43, P=0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT (chi(2)=7.62, P=0.007). In NT, plasma /"AM"/ concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of /"AM"/ gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes. | [
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"text_name": "AM"
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"entity_id": "C538228",
"entity_type": "Disease",
"text_name": "CA-repeat numbers"
} | No |
11467490 | New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3 mutation associated with craniosynostosis. | BACKGROUND: A large New Zealand Maori family has non-syndromic coronal craniosynostosis, which is inherited as an autosomal dominant mutation with variable expression. The aim of the study is to determine whether the family has the pro250arg mutation in the gene for fibroblast growth factor receptor 3 (FGFR3), a mutation found in patients with various types of craniosynostosis. PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom five have coronal synostosis. A family pedigree tracing six generations was recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14 family members. Polymerase chain reaction, restriction-enzyme digestion and DNA sequencing was performed to identify the pro250arg mutation in FGFR3. RESULTS: Seven family members were heterozygous for the pro250arg mutation in FGFR3. The mutation showed autosomal dominance with reduced penetrance and variable expressivity. CONCLUSION: Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses. | New Zealand Maori family with the pro250arg /"fibroblast growth factor receptor 3"/ mutation associated with /"craniosynostosis"/. | BACKGROUND: A large New Zealand Maori family has non-syndromic coronal craniosynostosis, which is inherited as an autosomal dominant mutation with variable expression. The aim of the study is to determine whether the family has the pro250arg mutation in the gene for /"fibroblast growth factor receptor 3"/ (/"FGFR3"/), a mutation found in patients with various types of /"craniosynostosis"/. PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom five have coronal synostosis. A family pedigree tracing six generations was recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14 family members. Polymerase chain reaction, restriction-enzyme digestion and DNA sequencing was performed to identify the pro250arg mutation in /"FGFR3"/. RESULTS: Seven family members were heterozygous for the pro250arg mutation in /"FGFR3"/. The mutation showed autosomal dominance with reduced penetrance and variable expressivity. CONCLUSION: Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of /"craniosynostoses"/. | [
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"text_name": "craniosynostosis"
} | Yes |
11467490 | New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3 mutation associated with craniosynostosis. | BACKGROUND: A large New Zealand Maori family has non-syndromic coronal craniosynostosis, which is inherited as an autosomal dominant mutation with variable expression. The aim of the study is to determine whether the family has the pro250arg mutation in the gene for fibroblast growth factor receptor 3 (FGFR3), a mutation found in patients with various types of craniosynostosis. PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom five have coronal synostosis. A family pedigree tracing six generations was recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14 family members. Polymerase chain reaction, restriction-enzyme digestion and DNA sequencing was performed to identify the pro250arg mutation in FGFR3. RESULTS: Seven family members were heterozygous for the pro250arg mutation in FGFR3. The mutation showed autosomal dominance with reduced penetrance and variable expressivity. CONCLUSION: Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses. | New Zealand Maori family with the pro250arg /"fibroblast growth factor receptor 3"/ mutation associated with craniosynostosis. | BACKGROUND: A large New Zealand Maori family has non-syndromic coronal craniosynostosis, which is inherited as an autosomal dominant mutation with variable expression. The aim of the study is to determine whether the family has the pro250arg mutation in the gene for /"fibroblast growth factor receptor 3"/ (/"FGFR3"/), a mutation found in patients with various types of craniosynostosis. PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom five have coronal /"synostosis"/. A family pedigree tracing six generations was recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14 family members. Polymerase chain reaction, restriction-enzyme digestion and DNA sequencing was performed to identify the pro250arg mutation in /"FGFR3"/. RESULTS: Seven family members were heterozygous for the pro250arg mutation in /"FGFR3"/. The mutation showed autosomal dominance with reduced penetrance and variable expressivity. CONCLUSION: Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses. | [
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} | No |
11472373 | Haemolytic onset of Wilson disease in a patient with homozygous truncation of ATP7B at Arg1319. | We describe a 19-year-old woman with haemolytic anaemia and thrombocytopenia as the initial manifestation of Wilson disease (WD). There are two reasons for reporting such an improbable case. First, it emphasizes the importance of recognizing atypical clinical presentations of potentially lethal recessive traits for which therapy is available. Second, it shows that, even in a monogenic disorder like WD, the phenotype cannot be extrapolated from the mutated genotype in a simple fashion; this patient had a relatively late-onset form of WD despite homozygosity for a genetic lesion leading to an apparent complete loss of function of the WD copper transporter. | Haemolytic onset of /"Wilson disease"/ in a patient with homozygous truncation of /"ATP7B"/ at Arg1319. | We describe a 19-year-old woman with haemolytic anaemia and thrombocytopenia as the initial manifestation of /"Wilson disease"/ (/"WD"/). There are two reasons for reporting such an improbable case. First, it emphasizes the importance of recognizing atypical clinical presentations of potentially lethal recessive traits for which therapy is available. Second, it shows that, even in a monogenic disorder like /"WD"/, the phenotype cannot be extrapolated from the mutated genotype in a simple fashion; this patient had a relatively late-onset form of /"WD"/ despite homozygosity for a genetic lesion leading to an apparent complete loss of function of the /"WD"/ copper transporter. | [
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} | Yes |
11472373 | Haemolytic onset of Wilson disease in a patient with homozygous truncation of ATP7B at Arg1319. | We describe a 19-year-old woman with haemolytic anaemia and thrombocytopenia as the initial manifestation of Wilson disease (WD). There are two reasons for reporting such an improbable case. First, it emphasizes the importance of recognizing atypical clinical presentations of potentially lethal recessive traits for which therapy is available. Second, it shows that, even in a monogenic disorder like WD, the phenotype cannot be extrapolated from the mutated genotype in a simple fashion; this patient had a relatively late-onset form of WD despite homozygosity for a genetic lesion leading to an apparent complete loss of function of the WD copper transporter. | Haemolytic onset of Wilson disease in a patient with homozygous truncation of /"ATP7B"/ at Arg1319. | We describe a 19-year-old woman with /"haemolytic anaemia"/ and thrombocytopenia as the initial manifestation of Wilson disease (WD). There are two reasons for reporting such an improbable case. First, it emphasizes the importance of recognizing atypical clinical presentations of potentially lethal recessive traits for which therapy is available. Second, it shows that, even in a monogenic disorder like WD, the phenotype cannot be extrapolated from the mutated genotype in a simple fashion; this patient had a relatively late-onset form of WD despite homozygosity for a genetic lesion leading to an apparent complete loss of function of the WD copper transporter. | [
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11474225 | Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. | Significance of /"ACE"/ genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of /"angiotensin-converting enzyme"/ (/"ACE"/) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of /"ACE"/ genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to /"end-stage renal failure"/ during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the /"ACE"/ gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). /"ACE"/ genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of /"end-stage renal failure"/ (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the /"ACE"/ gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of /"ACE"/ genotypes. | [
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] | {
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} | Yes |
11474225 | Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. | Significance of /"ACE"/ genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of /"angiotensin-converting enzyme"/ (/"ACE"/) genotypes and medical treatments in children with primary /"focal segmental glomerulosclerosis"/ (/"FSGS"/). METHODS: A multicenter retrospective study was performed on the role of /"ACE"/ genotypes and medical treatments in 43 Japanese children with /"FSGS"/ (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the /"ACE"/ gene was higher in the whole group of 43 children with /"FSGS"/ and in a subgroup of 28 steroid-resistant /"FSGS"/ children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). /"ACE"/ genotypes did not affect renal survival in the whole /"FSGS"/ group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with /"FSGS"/ showed that the D allele of the /"ACE"/ gene is associated with the development of /"FSGS"/, but not associated with the progression of /"FSGS"/ which was greatly ameliorated with ciclosporin, irrespective of /"ACE"/ genotypes. | [
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"text_name": "focal segmental glomerulosclerosis"
} | Yes |
11474225 | Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. | Significance of /"ACE"/ genotypes and medical treatments in childhood focal /"glomerulosclerosis"/. | BACKGROUND: There is little information on the significance of /"angiotensin-converting enzyme"/ (/"ACE"/) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of /"ACE"/ genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the /"ACE"/ gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). /"ACE"/ genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the /"ACE"/ gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of /"ACE"/ genotypes. | [
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} | No |
11474225 | Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis. | BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. | Significance of /"ACE"/ genotypes and medical treatments in childhood focal /"glomerulosclerosis"/. | BACKGROUND: There is little information on the significance of /"angiotensin-converting enzyme"/ (/"ACE"/) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of /"ACE"/ genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the /"ACE"/ gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). /"ACE"/ genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the /"ACE"/ gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of /"ACE"/ genotypes. | [
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} | No |
11517440 | Susceptibility to primary Epstein-Barr virus infection is associated with interleukin-10 gene promoter polymorphism. | In total, 116 children were investigated to determine whether the interleukin (IL)-10 polymorphism influences the age at primary Epstein-Barr virus (EBV) infection. The promoter of IL-10 is polymorphic, with 3 known single base substitutions (G/A at -1082, C/T at -819, and C/A at -592), which form 3 haplotypes: GCC, ACC, and ATA. This study found that carriage of the ATA haplotype protects against early EBV infection. The presence of the ATA haplotype was associated with EBV seronegativity (odds ratio, 2.6; 95% confidence interval, 1.04-6.7; P=.04), when controlled by age. To examine the effect of haplotypes on IL-10 production, IL-10 plasma levels were measured in 50 newborns and 400 adults and were correlated with the IL-10 haplotype. The IL-10 levels were significantly higher in the ATA carriers than in the noncarriers. These data suggest that the IL-10 ATA haplotype confers protection against primary EBV infection and that the effect is mediated by high IL-10 levels. | Susceptibility to primary /"Epstein-Barr virus infection"/ is associated with interleukin-10 gene promoter polymorphism. | In total, 116 children were investigated to determine whether the /"interleukin (IL)-10"/ polymorphism influences the age at primary /"Epstein-Barr virus (EBV) infection"/. The promoter of /"IL-10"/ is polymorphic, with 3 known single base substitutions (G/A at -1082, C/T at -819, and C/A at -592), which form 3 haplotypes: GCC, ACC, and ATA. This study found that carriage of the ATA haplotype protects against early /"EBV infection"/. The presence of the ATA haplotype was associated with EBV seronegativity (odds ratio, 2.6; 95% confidence interval, 1.04-6.7; P=.04), when controlled by age. To examine the effect of haplotypes on /"IL-10"/ production, /"IL-10"/ plasma levels were measured in 50 newborns and 400 adults and were correlated with the /"IL-10"/ haplotype. The /"IL-10"/ levels were significantly higher in the ATA carriers than in the noncarriers. These data suggest that the /"IL-10"/ ATA haplotype confers protection against primary /"EBV infection"/ and that the effect is mediated by high /"IL-10"/ levels. | [
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"text_name": "Epstein-Barr virus (EBV) infection"
} | Yes |
11553050 | PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation. | Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family. | /"PAX6"/ mutation in a family with /"aniridia"/, congenital ptosis, and mental retardation. | /"Congenital aniridia"/ is due to deletions and point mutations in the /"PAX6"/ gene. We describe here a case of a mother and her two sons with a syndrome comprising /"congenital aniridia"/, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the /"PAX6"/ locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the /"PAX6"/ gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for /"aniridia"/ and ptosis, and possibly also for the observed cognitive dysfunction in this family. | [
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} | {
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"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "Congenital aniridia"
} | Yes |
11553050 | PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation. | Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family. | /"PAX6"/ mutation in a family with aniridia, congenital ptosis, and /"mental retardation"/. | Congenital aniridia is due to deletions and point mutations in the /"PAX6"/ gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight /"mental retardation"/. The sons also show behavioral changes. The possibility of deletion around the /"PAX6"/ locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the /"PAX6"/ gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family. | [
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}
] | {
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} | {
"begin_idx": "64",
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"entity_id": "D008607",
"entity_type": "Disease",
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} | No |
11556548 | Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas. | Pilocytic astrocytomas classified as WHO grade I typically arise in childhood and upon complete surgical removal carry a favorable prognosis. Children with neurofibromatosis 1 (NF1) have a vastly increased risk for pilocytic astrocytomas, especially for those of the optic nerve. Using 4 intragenic NF1 microsatellite markers, we examined losses of NF1 alleles on the long arm of chromosome 17 in 12 NF1-associated and 25 sporadic pilocytic astrocytomas. The TP53 gene region on the short arm of chromosome 17 was also examined in these tumors using 3 markers. Loss of 1 NF1 allele was detected in 11 of 12 (92%) informative NF1-associated pilocytic astrocytomas. In contrast, only 1 of 24 informative (4%) sporadic pilocytic astrocytomas exhibited allelic loss in the NF1 region. Among the 11 NF1-associated tumors with NF1 loss, 5 had also lost alleles on 17p. The high rate of NF1 allele loss in NF1-associated pilocytic astrocytomas suggests a tumor initiating or promoting action of the NF1 gene in these patients. On the other hand, the much lower rate of NF1-allele loss in sporadic pilocytic astrocytomas argues for only minor importance of NF1 in that patient group. The present data support different mechanisms in the formation of NF1-associated and sporadic pilocytic astrocytomas. | Loss of /"NF1"/ alleles distinguish sporadic from /"NF1"/-associated /"pilocytic astrocytomas"/. | /"Pilocytic astrocytomas"/ classified as WHO grade I typically arise in childhood and upon complete surgical removal carry a favorable prognosis. Children with /"neurofibromatosis 1"/ (/"NF1"/) have a vastly increased risk for /"pilocytic astrocytomas"/, especially for those of the optic nerve. Using 4 intragenic /"NF1"/ microsatellite markers, we examined losses of /"NF1"/ alleles on the long arm of chromosome 17 in 12 /"NF1"/-associated and 25 sporadic /"pilocytic astrocytomas"/. The TP53 gene region on the short arm of chromosome 17 was also examined in these tumors using 3 markers. Loss of 1 /"NF1"/ allele was detected in 11 of 12 (92%) informative /"NF1"/-associated /"pilocytic astrocytomas"/. In contrast, only 1 of 24 informative (4%) sporadic /"pilocytic astrocytomas"/ exhibited allelic loss in the /"NF1"/ region. Among the 11 /"NF1"/-associated tumors with NF1 loss, 5 had also lost alleles on 17p. The high rate of /"NF1"/ allele loss in /"NF1"/-associated /"pilocytic astrocytomas"/ suggests a tumor initiating or promoting action of the /"NF1"/ gene in these patients. On the other hand, the much lower rate of /"NF1"/-allele loss in sporadic /"pilocytic astrocytomas"/ argues for only minor importance of /"NF1"/ in that patient group. The present data support different mechanisms in the formation of /"NF1"/-associated and sporadic /"pilocytic astrocytomas"/. | [
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11556548 | Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas. | Pilocytic astrocytomas classified as WHO grade I typically arise in childhood and upon complete surgical removal carry a favorable prognosis. Children with neurofibromatosis 1 (NF1) have a vastly increased risk for pilocytic astrocytomas, especially for those of the optic nerve. Using 4 intragenic NF1 microsatellite markers, we examined losses of NF1 alleles on the long arm of chromosome 17 in 12 NF1-associated and 25 sporadic pilocytic astrocytomas. The TP53 gene region on the short arm of chromosome 17 was also examined in these tumors using 3 markers. Loss of 1 NF1 allele was detected in 11 of 12 (92%) informative NF1-associated pilocytic astrocytomas. In contrast, only 1 of 24 informative (4%) sporadic pilocytic astrocytomas exhibited allelic loss in the NF1 region. Among the 11 NF1-associated tumors with NF1 loss, 5 had also lost alleles on 17p. The high rate of NF1 allele loss in NF1-associated pilocytic astrocytomas suggests a tumor initiating or promoting action of the NF1 gene in these patients. On the other hand, the much lower rate of NF1-allele loss in sporadic pilocytic astrocytomas argues for only minor importance of NF1 in that patient group. The present data support different mechanisms in the formation of NF1-associated and sporadic pilocytic astrocytomas. | Loss of NF1 alleles distinguish sporadic from NF1-associated /"pilocytic astrocytomas"/. | /"Pilocytic astrocytomas"/ classified as WHO grade I typically arise in childhood and upon complete surgical removal carry a favorable prognosis. Children with neurofibromatosis 1 (NF1) have a vastly increased risk for /"pilocytic astrocytomas"/, especially for those of the optic nerve. Using 4 intragenic NF1 microsatellite markers, we examined losses of NF1 alleles on the long arm of chromosome 17 in 12 NF1-associated and 25 sporadic /"pilocytic astrocytomas"/. The /"TP53"/ gene region on the short arm of chromosome 17 was also examined in these tumors using 3 markers. Loss of 1 NF1 allele was detected in 11 of 12 (92%) informative NF1-associated /"pilocytic astrocytomas"/. In contrast, only 1 of 24 informative (4%) sporadic /"pilocytic astrocytomas"/ exhibited allelic loss in the NF1 region. Among the 11 NF1-associated tumors with NF1 loss, 5 had also lost alleles on 17p. The high rate of NF1 allele loss in NF1-associated /"pilocytic astrocytomas"/ suggests a tumor initiating or promoting action of the NF1 gene in these patients. On the other hand, the much lower rate of NF1-allele loss in sporadic /"pilocytic astrocytomas"/ argues for only minor importance of NF1 in that patient group. The present data support different mechanisms in the formation of NF1-associated and sporadic /"pilocytic astrocytomas"/. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous /"liver diseases"/, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous /"liver diseases"/, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on /"iron overload disorders"/ in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with /"chronic hepatitis C"/, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with /"chronic hepatitis C"/ was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with /"chronic hepatitis C"/, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or /"chronic hepatitis C"/. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for /"hereditary hemochromatosis"/ close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary /"hemochromatosis"/, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with /"hemochromatosis"/ had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with /"hemochromatosis"/ or chronic hepatitis C. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with /"alcoholic liver disease"/ were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with /"alcoholic liver disease"/ were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with /"alcoholic liver disease"/ were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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"entity_type": "Disease",
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11579943 | C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C. | C282Y and H63D mutations in the /"HFE"/ gene have no effect on iron overload disorders in Japan. | OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as /"HFE"/. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of /"HFE"/, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with /"alcoholic liver disease"/ were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in /"HFE"/ affect Japanese patients with hemochromatosis or chronic hepatitis C. | [
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11583755 | MHC class II region, CTLA4 gene, and ophthalmopathy in patients with Graves' disease. | Up to half of patients with Graves' hyperthyroidism have signs of thyroid associated ophthalmopathy, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for Graves' disease in ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4 (CTLA4) gene. Allelic frequencies of these genes in patients with Graves' disease who did and did not have concurrent thyroid-associated ophthalmopathy did not differ, and are, therefore, unlikely to contribute to its development. | MHC class II region, /"CTLA4"/ gene, and ophthalmopathy in patients with /"Graves' disease"/. | Up to half of patients with Graves' hyperthyroidism have signs of thyroid associated ophthalmopathy, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for /"Graves' disease"/ in ophthalmopathy; the MHC class II region and the /"cytotoxic T lymphocyte antigen-4"/ (/"CTLA4"/) gene. Allelic frequencies of these genes in patients with /"Graves' disease"/ who did and did not have concurrent thyroid-associated ophthalmopathy did not differ, and are, therefore, unlikely to contribute to its development. | [
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11583755 | MHC class II region, CTLA4 gene, and ophthalmopathy in patients with Graves' disease. | Up to half of patients with Graves' hyperthyroidism have signs of thyroid associated ophthalmopathy, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for Graves' disease in ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4 (CTLA4) gene. Allelic frequencies of these genes in patients with Graves' disease who did and did not have concurrent thyroid-associated ophthalmopathy did not differ, and are, therefore, unlikely to contribute to its development. | MHC class II region, /"CTLA4"/ gene, and /"ophthalmopathy"/ in patients with Graves' disease. | Up to half of patients with Graves' hyperthyroidism have signs of /"thyroid associated ophthalmopathy"/, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for Graves' disease in /"ophthalmopathy"/; the MHC class II region and the /"cytotoxic T lymphocyte antigen-4"/ (/"CTLA4"/) gene. Allelic frequencies of these genes in patients with Graves' disease who did and did not have concurrent /"thyroid-associated ophthalmopathy"/ did not differ, and are, therefore, unlikely to contribute to its development. | [
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11641043 | Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the transforming growth factor beta1 (TGF-beta1) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of TGF-beta1 in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that tumors in heterozygous TGF-beta1 mice might be more likely to have K-ras mutations compared with tumors in wildtype TGF-beta1 mice. Urethane-induced lung tumors in AJBL6 TGF-beta1 +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both TGF-beta1 genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | Heterozygous inactivation of /"TGF-beta1"/ increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the /"transforming growth factor beta1"/ (/"TGF-beta1"/) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of /"TGF-beta1"/ in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse /"lung tumors"/, we postulated that tumors in heterozygous /"TGF-beta1"/ mice might be more likely to have K-ras mutations compared with tumors in wildtype /"TGF-beta1"/ mice. Urethane-induced /"lung tumors"/ in AJBL6 /"TGF-beta1"/ +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both /"TGF-beta1"/ genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of /"TGF-beta1"/+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | [
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11641043 | Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the transforming growth factor beta1 (TGF-beta1) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of TGF-beta1 in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that tumors in heterozygous TGF-beta1 mice might be more likely to have K-ras mutations compared with tumors in wildtype TGF-beta1 mice. Urethane-induced lung tumors in AJBL6 TGF-beta1 +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both TGF-beta1 genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of /"K-ras"/. | Mice heterozygous for deletion of the transforming growth factor beta1 (TGF-beta1) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of TGF-beta1 in epithelial cells is associated with /"K-ras"/ p21, and /"K-ras"/ mutations commonly occur in chemically-induced mouse /"lung tumors"/, we postulated that tumors in heterozygous TGF-beta1 mice might be more likely to have /"K-ras"/ mutations compared with tumors in wildtype TGF-beta1 mice. Urethane-induced /"lung tumors"/ in AJBL6 TGF-beta1 +/- and +/+ mice were examined for /"K-ras"/ mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both TGF-beta1 genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with /"K-ras"/ mutations. | [
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11641043 | Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the transforming growth factor beta1 (TGF-beta1) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of TGF-beta1 in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that tumors in heterozygous TGF-beta1 mice might be more likely to have K-ras mutations compared with tumors in wildtype TGF-beta1 mice. Urethane-induced lung tumors in AJBL6 TGF-beta1 +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both TGF-beta1 genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | Heterozygous inactivation of /"TGF-beta1"/ increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the /"transforming growth factor beta1"/ (/"TGF-beta1"/) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of /"TGF-beta1"/ in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that tumors in heterozygous /"TGF-beta1"/ mice might be more likely to have K-ras mutations compared with tumors in wildtype /"TGF-beta1"/ mice. Urethane-induced lung tumors in AJBL6 /"TGF-beta1"/ +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ /"carcinomas"/, but in only 50% of the adenomas of both /"TGF-beta1"/ genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, /"carcinomas"/ with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of /"TGF-beta1"/+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | [
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11641043 | Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the transforming growth factor beta1 (TGF-beta1) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of TGF-beta1 in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that tumors in heterozygous TGF-beta1 mice might be more likely to have K-ras mutations compared with tumors in wildtype TGF-beta1 mice. Urethane-induced lung tumors in AJBL6 TGF-beta1 +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- tumors (67%) and 10/16 +/+ tumors (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both TGF-beta1 genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ tumors. Three +/- (17%) and three +/+ (19%) tumors showed codon 12 mutations, mostly G-->A transitions. Two +/- tumors had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of TGF-beta1+/- mice to urethane-induced lung carcinogenesis does not involve selective development of tumors with K-ras mutations. | Heterozygous inactivation of /"TGF-beta1"/ increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras. | Mice heterozygous for deletion of the /"transforming growth factor beta1"/ (/"TGF-beta1"/) gene show an enhanced rate of lung tumorigenesis following carcinogen treatment. Since the growth inhibitory activity of /"TGF-beta1"/ in epithelial cells is associated with K-ras p21, and K-ras mutations commonly occur in chemically-induced mouse lung tumors, we postulated that /"tumors"/ in heterozygous /"TGF-beta1"/ mice might be more likely to have K-ras mutations compared with /"tumors"/ in wildtype /"TGF-beta1"/ mice. Urethane-induced lung tumors in AJBL6 /"TGF-beta1"/ +/- and +/+ mice were examined for K-ras mutations by polymerase chain reaction/single strand conformation polymorphism analysis and sequencing. Mutation frequencies were similar in both genotypes: 12/18 +/- /"tumors"/ (67%) and 10/16 +/+ /"tumors"/ (62%). Mutations occurred in 80% +/- and 75% +/+ carcinomas, but in only 50% of the adenomas of both /"TGF-beta1"/ genotypes. Codon 61 A-->G transition mutations were predominant, occurring in 61% +/- and 44% +/+ /"tumors"/. Three +/- (17%) and three +/+ (19%) /"tumors"/ showed codon 12 mutations, mostly G-->A transitions. Two +/- /"tumors"/ had both codon 61 and codon 12 mutations. Interestingly, carcinomas with mutations in codon 61 were larger than those with codon 12 changes. It appears that the mechanism of enhanced susceptibility of /"TGF-beta1"/+/- mice to urethane-induced lung carcinogenesis does not involve selective development of /"tumors"/ with K-ras mutations. | [
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11709213 | Neuropeptide Y, peptide YY and aluminum in Alzheimer's disease: is there an etiological relationship? | Neuropeptide Y (NPY) and peptide YY (PYY) are members of the pancreatic polypeptide family which have a high degree of primary and tertiary structural homology. They function as neurotransmitters and humoral agents in central nervous system and gastrointestinal function. During the last two decades, NPY body fluid concentrations and NPY/PYY brain receptor numbers have been demonstrated to be altered during the course of Alzheimer's disease. Recent research has shown that both NPY and PYY may be involved in aluminum metabolism in animal models. A brief discussion of the structure, biological activity and possible involvement of these peptides in aluminum metabolism and Alzheimer's disease is contained herein. | Neuropeptide Y, /"peptide YY"/ and aluminum in /"Alzheimer's disease"/: is there an etiological relationship? | Neuropeptide Y (NPY) and /"peptide YY"/ (/"PYY"/) are members of the pancreatic polypeptide family which have a high degree of primary and tertiary structural homology. They function as neurotransmitters and humoral agents in central nervous system and gastrointestinal function. During the last two decades, NPY body fluid concentrations and NPY//"PYY"/ brain receptor numbers have been demonstrated to be altered during the course of /"Alzheimer's disease"/. Recent research has shown that both NPY and /"PYY"/ may be involved in aluminum metabolism in animal models. A brief discussion of the structure, biological activity and possible involvement of these peptides in aluminum metabolism and /"Alzheimer's disease"/ is contained herein. | [
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11712802 | An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group. | Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required. | An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group. | Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 /"neutropenia"/ occurred only in 2 (5.2%) patients. Five patients experienced /"febrile neutropenia"/, which was successfully treated with /"G-CSF"/ and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, /"GSTM1"/, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, /"GSTM1"/, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, /"CYP2E1"/, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the /"CYP1A1"/, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the /"CYP1A1"/ gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and /"hOGG1"/ genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and /"hOGG1"/ polymorphisms. However, one novel polymorphism/mutation of the /"hOGG1"/ gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, /"NAT2"/, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, /"NAT1"/, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, /"MnSOD"/, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the /"MnSOD"/, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the /"tumor"/ from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. Polymorphisms of the CYP1A1, /"CYP2E1"/, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the /"tumor"/ from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and /"hOGG1"/ genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and /"hOGG1"/ polymorphisms. However, one novel polymorphism/mutation of the /"hOGG1"/ gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and /"K-ras"/ mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the /"tumor"/ from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the /"K-ras"/ gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the /"K-ras"/ mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and /"K-ras"/ mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the /"tumor"/ from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the /"K-ras"/ gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the /"K-ras"/ mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the /"tumor"/ from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, /"tumors"/, and controls, respectively. Polymorphisms of the /"CYP1A1"/, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the /"CYP1A1"/ gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and /"K-ras"/ mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the /"K-ras"/ gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the /"K-ras"/ mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11719088 | DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 pancreatic tumors and 13 normal tissues adjacent to the tumor from patients with pancreatic cancer. Normal pancreatic tissues from 24 organ donors, from six patients with non-pancreatic cancers, and from five patients with chronic pancreatitis served as controls. It was found that tissue samples from patients with pancreatic cancer had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a pancreatic tumor. Mutation at codon 12 of the K-ras gene was found in 25 (81%) of 31 pancreatic tumors, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the K-ras mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in pancreatic carcinogenesis. | DNA adducts, genetic polymorphisms, and /"K-ras"/ mutation in human /"pancreatic cancer"/. | To test the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/ in susceptible individuals, aromatic DNA adducts and 8-hydroxyguanosine (8-OH-dG) were measured by (32)P-postlabeling and HPLC-EC, respectively, in 31 /"pancreatic tumors"/ and 13 normal tissues adjacent to the tumor from patients with /"pancreatic cancer"/. Normal pancreatic tissues from 24 organ donors, from six patients with /"non-pancreatic cancers"/, and from five patients with chronic /"pancreatitis"/ served as controls. It was found that tissue samples from patients with /"pancreatic cancer"/ had significantly higher levels of both aromatic DNA adducts and 8-OH-dG compared with control samples. The mean (+/-S.D.) levels of aromatic DNA adducts were 101.8+/-74.6, 26.9+/-26.6, and 11.2+/-6.6 per 10(9) nucleotides in adjacent tissues, tumors, and controls, respectively. The mean (+/-S.D.) levels of 8-OH-dG were 11.9+/-9.6, 10.8+/-10.6, and 6.7+/-4.6 per 10(5) nucleotides in adjacent tissues, tumors, and controls, respectively. Polymorphisms of the CYP1A1, CYP2E1, NAT1, NAT2, GSTM1, MnSOD, and hOGG1 genes were determined in these patients. The level of aromatic DNA adducts was significantly associated with polymorphism of the CYP1A1 gene. No significant correlation was found between the level of 8-OH-dG and the MnSOD, GSTM1, and hOGG1 polymorphisms. However, one novel polymorphism/mutation of the hOGG1 gene was found in a /"pancreatic tumor"/. Mutation at codon 12 of the /"K-ras"/ gene was found in 25 (81%) of 31 /"pancreatic tumors"/, including three G-to-A transitions and 22 G-to-T transversions. Patients with the G-to-T mutation had a significantly higher level of aromatic DNA adducts than those with G-to-A or wild-type codon (P=0.02). On the other hand, the /"K-ras"/ mutation profile was not related to the level of 8-OH-dG. Given the limitation of sample size, these preliminary data lend further support the hypothesis that carcinogen exposure and oxidative stress are involved in /"pancreatic carcinogenesis"/. | [
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11730829 | Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study. | In order to characterize the lipoprotein abnormalities in familial combined hyperlipidemia (FCHL) and to describe factors associated with the stability of the FCHL phenotype during 20-year follow-up, 287 individuals from 48 families with FCHL originally identified in the early 1970s (baseline) were studied. Hyperlipidemia was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), apolipoprotein (apo) A-I, apoB, and apoE polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with hyperlipidemia at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent hyperlipidemia. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of hyperlipidemia over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and apoE alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with hyperlipidemia and apoE polymorphism is associated with later onset of hyperlipidemia in FCHL. | Lipoprotein and apolipoprotein abnormalities in /"familial combined hyperlipidemia"/: a 20-year prospective study. | In order to characterize the lipoprotein abnormalities in /"familial combined hyperlipidemia"/ (/"FCHL"/) and to describe factors associated with the stability of the /"FCHL"/ phenotype during 20-year follow-up, 287 individuals from 48 families with /"FCHL"/ originally identified in the early 1970s (baseline) were studied. Hyperlipidemia was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), apolipoprotein (apo) A-I, apoB, and /"apoE"/ polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with hyperlipidemia at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent hyperlipidemia. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of hyperlipidemia over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and /"apoE"/ alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with hyperlipidemia and /"apoE"/ polymorphism is associated with later onset of hyperlipidemia in /"FCHL"/. | [
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11730829 | Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study. | In order to characterize the lipoprotein abnormalities in familial combined hyperlipidemia (FCHL) and to describe factors associated with the stability of the FCHL phenotype during 20-year follow-up, 287 individuals from 48 families with FCHL originally identified in the early 1970s (baseline) were studied. Hyperlipidemia was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), apolipoprotein (apo) A-I, apoB, and apoE polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with hyperlipidemia at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent hyperlipidemia. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of hyperlipidemia over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and apoE alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with hyperlipidemia and apoE polymorphism is associated with later onset of hyperlipidemia in FCHL. | Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study. | In order to characterize the lipoprotein abnormalities in familial combined hyperlipidemia (FCHL) and to describe factors associated with the stability of the FCHL phenotype during 20-year follow-up, 287 individuals from 48 families with FCHL originally identified in the early 1970s (baseline) were studied. /"Hyperlipidemia"/ was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), /"apolipoprotein (apo) A-I"/, apoB, and apoE polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with /"hyperlipidemia"/ at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent /"hyperlipidemia"/. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of /"hyperlipidemia"/ over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and apoE alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with /"hyperlipidemia"/ and apoE polymorphism is associated with later onset of /"hyperlipidemia"/ in FCHL. | [
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11739440 | Insulin gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence. | Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the insulin gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious pubarche, hyperinsulinemia was assessed from mean insulin levels during an oral glucose load (MSI), and insulin sensitivity was determined from fasting glucose and insulin levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious pubarche and control girls. However among precocious pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and lower insulin sensitivity (P < 0.005) than III/III girls. In precocious pubarche girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with precocious pubarche, hyperinsulinemia and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | /"Insulin"/ gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and /"hyperinsulinism"/ sequence. | Low birth weight associations with /"hyperinsulinemia"/ and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the /"insulin"/ gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious pubarche, /"hyperinsulinemia"/ was assessed from mean /"insulin"/ levels during an oral glucose load (MSI), and /"insulin"/ sensitivity was determined from fasting glucose and /"insulin"/ levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious pubarche and control girls. However among precocious pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and lower insulin sensitivity (P < 0.005) than III/III girls. In precocious pubarche girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with precocious pubarche, /"hyperinsulinemia"/ and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | [
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11739440 | Insulin gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence. | Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the insulin gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious pubarche, hyperinsulinemia was assessed from mean insulin levels during an oral glucose load (MSI), and insulin sensitivity was determined from fasting glucose and insulin levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious pubarche and control girls. However among precocious pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and lower insulin sensitivity (P < 0.005) than III/III girls. In precocious pubarche girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with precocious pubarche, hyperinsulinemia and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | /"Insulin"/ gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence. | Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the /"insulin"/ gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious pubarche, hyperinsulinemia was assessed from mean /"insulin"/ levels during an oral glucose load (MSI), and /"insulin"/ sensitivity was determined from fasting glucose and /"insulin"/ levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious pubarche and control girls. However among precocious pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and /"lower insulin sensitivity (P < 0.005) than III/III girls"/. In precocious pubarche girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with precocious pubarche, hyperinsulinemia and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | [
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11739440 | Insulin gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence. | Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with precocious pubarche (pubic hair <8 yr). We hypothesized that these associations might be influenced by the insulin gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with precocious pubarche, hyperinsulinemia was assessed from mean insulin levels during an oral glucose load (MSI), and insulin sensitivity was determined from fasting glucose and insulin levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in precocious pubarche girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in precocious pubarche and control girls. However among precocious pubarche girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and lower insulin sensitivity (P < 0.005) than III/III girls. In precocious pubarche girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with precocious pubarche, hyperinsulinemia and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | /"Insulin"/ gene variable number of tandem repeat genotype and the low birth weight, /"precocious pubarche"/, and hyperinsulinism sequence. | Low birth weight associations with hyperinsulinemia and other adulthood disease risk factors have been described in several cohorts, including girls who present with /"precocious pubarche"/ (pubic hair <8 yr). We hypothesized that these associations might be influenced by the /"insulin"/ gene (INS) variable number of tandem repeat (VNTR), a common polymorphism related to INS transcription levels. In 141 Caucasian girls, who presented with /"precocious pubarche"/, hyperinsulinemia was assessed from mean /"insulin"/ levels during an oral glucose load (MSI), and /"insulin"/ sensitivity was determined from fasting glucose and /"insulin"/ levels. Fasting blood lipid profiles were also measured. DNA was genotyped for INS VNTR allele class (I or III) in /"precocious pubarche"/ girls and in 140 age- and body mass index-matched control girls. INS VNTR genotype distribution was similar in /"precocious pubarche"/ and control girls. However among /"precocious pubarche"/ girls, INS VNTR genotype was related to the severity of phenotype; I/I and I/III genotypes had lower birth weights (P < 0.01), higher MSI (P < 0.005), and lower insulin sensitivity (P < 0.005) than III/III girls. In /"precocious pubarche"/ girls, birth weight was also inversely related to MSI (r = -0.29; P < 0.0005), total cholesterol (r = -0.38; P < 0.0005), and low density lipoprotein cholesterol (r = -0.44; P < 0.0005). Using logistic regression, additive adverse effects of I/* genotype and low birth weight were seen on MSI (P = 0.03 and P = 0.004, respectively) and total cholesterol levels (P = 0.01 and P < 0.0001). In summary, in girls who presented with /"precocious pubarche"/, hyperinsulinemia and dyslipidemia were related to both low birth weight and INS VNTR class I alleles. A similar interaction between genotype and intrauterine growth restraint may underlie other reported links between low birth weight and adulthood disease risks. | [
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