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12140789 | Genetic predisposition to obesity in bulimia nervosa: a mutation screen of the melanocortin-4 receptor gene. | Obesity has been identified as a risk factor for the development of bulimia nervosa (BN). Accordingly, we hypothesize that genotypes predisposing to obesity can be detected in patients with this eating disorder. In order to investigate this hypothesis we screened the melanocortin-4 receptor gene (MC4R) for mutations using single strand conformation analysis in 81 female inpatients treated for BN. A single patient with both extreme obesity and BN had a haplo-insufficiency mutation in the MC4R. Comparison of current and maximal body mass index (BMI) of all patients with cross-sectionally obtained BMI in the general population revealed an age appropriate distribution for current BMI and a substantially increased frequency for overweight at time of maximal BMI. Our findings suggest that overweight is a risk factor for BN in clinically ascertained patients. For the first time a genotype predisposing to obesity has been detected in an extremely obese patient with BN. | Genetic predisposition to obesity in bulimia nervosa: a mutation screen of the /"melanocortin-4 receptor"/ gene. | Obesity has been identified as a risk factor for the development of bulimia nervosa (BN). Accordingly, we hypothesize that genotypes predisposing to obesity can be detected in patients with this /"eating disorder"/. In order to investigate this hypothesis we screened the /"melanocortin-4 receptor"/ gene (/"MC4R"/) for mutations using single strand conformation analysis in 81 female inpatients treated for BN. A single patient with both extreme obesity and BN had a haplo-insufficiency mutation in the /"MC4R"/. Comparison of current and maximal body mass index (BMI) of all patients with cross-sectionally obtained BMI in the general population revealed an age appropriate distribution for current BMI and a substantially increased frequency for overweight at time of maximal BMI. Our findings suggest that overweight is a risk factor for BN in clinically ascertained patients. For the first time a genotype predisposing to obesity has been detected in an extremely obese patient with BN. | [
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12142547 | A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence. | BACKGROUND: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Qu bec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In obese subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans. | A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence. | BACKGROUND: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse /"MC3R"/ in body composition. To verify a possible similar effect of /"MC3R"/ in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Qu bec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete /"MC3R"/ cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of /"MC3R"/. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC /"MC3R"/ polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In /"obese"/ subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC /"MC3R"/ polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans. | [
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12142547 | A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence. | BACKGROUND: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Qu bec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In obese subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans. | A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence. | BACKGROUND: The melanocortin system includes five receptors (/"MC1R"/ to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Qu bec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In /"obese"/ subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans. | [
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12150336 | Calcium-sensing receptor gene polymorphisms in primary hyperparathyroidism. | The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing primary hyperparathyroidism (PHPT). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011 E) in patients with PHPT and their effect on its phenotype. We studied 103 Italian patients with PHPT and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 PHPT patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between PHPT patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian PHPT patients and the allotype AS does not appear to play a relevant role in the pathogenesis of PHPT and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects. | /"Calcium-sensing receptor"/ gene polymorphisms in /"primary hyperparathyroidism"/. | The /"calcium-sensing receptor"/ (/"CaR"/) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing /"primary hyperparathyroidism"/ (/"PHPT"/). The aim of the present study was to investigate the frequency of this and other 2 known /"CaR"/ polymorphisms (R990G and Q1011 E) in patients with /"PHPT"/ and their effect on its phenotype. We studied 103 Italian patients with /"PHPT"/ and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the /"CaR"/ gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 /"PHPT"/ patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 /"CaR"/ polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between /"PHPT"/ patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S /"CaR"/ polymorphism is the most common in Italian /"PHPT"/ patients and the allotype AS does not appear to play a relevant role in the pathogenesis of /"PHPT"/ and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects. | [
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12150336 | Calcium-sensing receptor gene polymorphisms in primary hyperparathyroidism. | The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing primary hyperparathyroidism (PHPT). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011 E) in patients with PHPT and their effect on its phenotype. We studied 103 Italian patients with PHPT and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 PHPT patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between PHPT patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian PHPT patients and the allotype AS does not appear to play a relevant role in the pathogenesis of PHPT and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects. | Calcium-sensing receptor gene polymorphisms in /"primary hyperparathyroidism"/. | The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing /"primary hyperparathyroidism"/ (/"PHPT"/). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011 E) in patients with /"PHPT"/ and their effect on its phenotype. We studied 103 Italian patients with /"PHPT"/ and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and /"PTH"/ levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 /"PHPT"/ patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between /"PHPT"/ patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian /"PHPT"/ patients and the allotype AS does not appear to play a relevant role in the pathogenesis of /"PHPT"/ and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects. | [
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12165742 | Meta-analysis of 20 case-control studies on the N-acetyltransferase 2 acetylation status and colorectal cancer risk. | BACKGROUND: Rapid NAT2 acetylation has been considered as a risk factor for developing colon cancer in a number of studies, however the overall results of such studies are inconsistent. To clarify the influence of NAT2 rapid acetylation status on colon cancer risk, we have performed a meta-analysis of 20 published case-control studies (4431 cases, 4547 controls). MATERIAL/METHODS: Odd ratio was employed to evaluate the risk of colon cancer and NAT2 rapid acetylation status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. The summary odds ratios were assessed by calculating a weighted average of odds ratios for all of the studies. RESULTS: The pooling of studies based on phenotyping methods indicated that the overall odds ratio of colon cancer risk associated with rapid acetylator was 1.51 (95%CI: 1.07-2.12). However, the risk of colon cancer associated with rapid acetylator from the studies based on genotyping method was lower with a calculated overall odds ratio of 1.06 (95%CI: 0.97-1.15). Pooling studies were also conducted on specific tumour sites and ethnic groups. The results show that effect of rapid acetylator on colon cancer risk was not obviously different. CONCLUSIONS: The results of our meta-analyses do not support the hypothesis that NAT2 alone is an important risk factor for colon cancer and suggests that NAT2 rapid acetylation status has no specific effect on the risk of developing colon cancer. | Meta-analysis of 20 case-control studies on the /"N-acetyltransferase 2"/ acetylation status and /"colorectal cancer"/ risk. | BACKGROUND: Rapid /"NAT2"/ acetylation has been considered as a risk factor for developing colon cancer in a number of studies, however the overall results of such studies are inconsistent. To clarify the influence of /"NAT2"/ rapid acetylation status on colon cancer risk, we have performed a meta-analysis of 20 published case-control studies (4431 cases, 4547 controls). MATERIAL/METHODS: Odd ratio was employed to evaluate the risk of colon cancer and /"NAT2"/ rapid acetylation status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. The summary odds ratios were assessed by calculating a weighted average of odds ratios for all of the studies. RESULTS: The pooling of studies based on phenotyping methods indicated that the overall odds ratio of colon cancer risk associated with rapid acetylator was 1.51 (95%CI: 1.07-2.12). However, the risk of colon cancer associated with rapid acetylator from the studies based on genotyping method was lower with a calculated overall odds ratio of 1.06 (95%CI: 0.97-1.15). Pooling studies were also conducted on specific tumour sites and ethnic groups. The results show that effect of rapid acetylator on colon cancer risk was not obviously different. CONCLUSIONS: The results of our meta-analyses do not support the hypothesis that /"NAT2"/ alone is an important risk factor for colon cancer and suggests that /"NAT2"/ rapid acetylation status has no specific effect on the risk of developing colon cancer. | [
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12165742 | Meta-analysis of 20 case-control studies on the N-acetyltransferase 2 acetylation status and colorectal cancer risk. | BACKGROUND: Rapid NAT2 acetylation has been considered as a risk factor for developing colon cancer in a number of studies, however the overall results of such studies are inconsistent. To clarify the influence of NAT2 rapid acetylation status on colon cancer risk, we have performed a meta-analysis of 20 published case-control studies (4431 cases, 4547 controls). MATERIAL/METHODS: Odd ratio was employed to evaluate the risk of colon cancer and NAT2 rapid acetylation status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. The summary odds ratios were assessed by calculating a weighted average of odds ratios for all of the studies. RESULTS: The pooling of studies based on phenotyping methods indicated that the overall odds ratio of colon cancer risk associated with rapid acetylator was 1.51 (95%CI: 1.07-2.12). However, the risk of colon cancer associated with rapid acetylator from the studies based on genotyping method was lower with a calculated overall odds ratio of 1.06 (95%CI: 0.97-1.15). Pooling studies were also conducted on specific tumour sites and ethnic groups. The results show that effect of rapid acetylator on colon cancer risk was not obviously different. CONCLUSIONS: The results of our meta-analyses do not support the hypothesis that NAT2 alone is an important risk factor for colon cancer and suggests that NAT2 rapid acetylation status has no specific effect on the risk of developing colon cancer. | Meta-analysis of 20 case-control studies on the /"N-acetyltransferase 2"/ acetylation status and colorectal cancer risk. | BACKGROUND: Rapid /"NAT2"/ acetylation has been considered as a risk factor for developing /"colon cancer"/ in a number of studies, however the overall results of such studies are inconsistent. To clarify the influence of /"NAT2"/ rapid acetylation status on /"colon cancer"/ risk, we have performed a meta-analysis of 20 published case-control studies (4431 cases, 4547 controls). MATERIAL/METHODS: Odd ratio was employed to evaluate the risk of /"colon cancer"/ and /"NAT2"/ rapid acetylation status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. The summary odds ratios were assessed by calculating a weighted average of odds ratios for all of the studies. RESULTS: The pooling of studies based on phenotyping methods indicated that the overall odds ratio of /"colon cancer"/ risk associated with rapid acetylator was 1.51 (95%CI: 1.07-2.12). However, the risk of /"colon cancer"/ associated with rapid acetylator from the studies based on genotyping method was lower with a calculated overall odds ratio of 1.06 (95%CI: 0.97-1.15). Pooling studies were also conducted on specific tumour sites and ethnic groups. The results show that effect of rapid acetylator on /"colon cancer"/ risk was not obviously different. CONCLUSIONS: The results of our meta-analyses do not support the hypothesis that /"NAT2"/ alone is an important risk factor for /"colon cancer"/ and suggests that /"NAT2"/ rapid acetylation status has no specific effect on the risk of developing /"colon cancer"/. | [
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12167522 | Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder. | INTRODUCTION: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the 5-HT2A receptor gene (HTR2A) contributes to both SAD and ADHD. The current study investigated whether variation in HTR2A was associated with symptoms of childhood ADHD in adult women with SAD. METHOD: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD. LIMITATIONS: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in HTR2A, childhood ADHD, and the later development of SAD in women. | Polymorphism of the /"serotonin-2A receptor"/ gene (/"HTR2A"/) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with /"seasonal affective disorder"/. | INTRODUCTION: Several lines of research point to a possible overlap between /"seasonal affective disorder"/ (/"SAD"/) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the /"5-HT2A receptor"/ gene (/"HTR2A"/) contributes to both /"SAD"/ and ADHD. The current study investigated whether variation in /"HTR2A"/ was associated with symptoms of childhood ADHD in adult women with /"SAD"/. METHOD: Sixty-six women with /"SAD"/ were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of /"SAD"/. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD. LIMITATIONS: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in /"HTR2A"/, childhood ADHD, and the later development of /"SAD"/ in women. | [
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12167522 | Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder. | INTRODUCTION: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the 5-HT2A receptor gene (HTR2A) contributes to both SAD and ADHD. The current study investigated whether variation in HTR2A was associated with symptoms of childhood ADHD in adult women with SAD. METHOD: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD. LIMITATIONS: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in HTR2A, childhood ADHD, and the later development of SAD in women. | Polymorphism of the /"serotonin-2A receptor"/ gene (/"HTR2A"/) associated with childhood /"attention deficit hyperactivity disorder"/ (/"ADHD"/) in adult women with seasonal affective disorder. | INTRODUCTION: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and /"attention deficit hyperactivity disorder"/ (/"ADHD"/), particularly in females. There is also emerging evidence that variation of the /"5-HT2A receptor"/ gene (/"HTR2A"/) contributes to both SAD and /"ADHD"/. The current study investigated whether variation in /"HTR2A"/ was associated with symptoms of childhood /"ADHD"/ in adult women with SAD. METHOD: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood /"ADHD"/, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood /"ADHD"/. LIMITATIONS: The current sample size is small, and childhood /"ADHD"/ diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in /"HTR2A"/, childhood /"ADHD"/, and the later development of SAD in women. | [
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12168876 | Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer. | We have identified two novel polymorphisms in the prostate-specific antigen (PSA) gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher PSA expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the PSA genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the PSA promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor. | Correlation of /"prostate-specific antigen"/ promoter polymorphisms with clinicopathological characteristics in /"breast cancer"/. | We have identified two novel polymorphisms in the /"prostate-specific antigen (PSA)"/ gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher /"PSA"/ expressions. We hypothesize that allelic differences may be associated with different phenotypes of /"breast cancer"/. To test this hypothesis, we assayed the /"PSA"/ genotype for 101 /"breast cancer"/ cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the /"PSA"/ promoter region is associated with /"less aggressive forms of breast cancer"/ and could be looked on as a favorable prognostic factor. | [
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12168876 | Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer. | We have identified two novel polymorphisms in the prostate-specific antigen (PSA) gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher PSA expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the PSA genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the PSA promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor. | Correlation of /"prostate-specific antigen"/ promoter polymorphisms with clinicopathological characteristics in breast cancer. | We have identified two novel polymorphisms in the /"prostate-specific antigen (PSA)"/ gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in /"tumors"/ with higher /"PSA"/ expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the /"PSA"/ genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the /"tumors"/. At the time of diagnosis, the A-AA allele occurred more frequently in the /"tumors"/ characterized by small /"tumor"/ size, good to moderate differentiation, p53-negativity and low /"tumor"/ proliferation activity. Our results suggest that the presence of the A-AA allele at the /"PSA"/ promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor. | [
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} | No |
12170472 | [Genetic polymorphism of UDP-glucuronosyltransferase 1F and susceptibility to hepatocellular carcinoma]. | OBJECTIVE: To study the genetic polymorphisms of UDP-glucuronosyltransferase 1F(UGT1F) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC). METHODS: The polymorphisms of UGT1F of 84 patients with HCC and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing. RESULTS: Three new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of UGT1F in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant. CONCLUSION: Exons 2-5 of UGT1F are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with HCC. | [Genetic polymorphism of /"UDP-glucuronosyltransferase 1F"/ and susceptibility to /"hepatocellular carcinoma"/]. | OBJECTIVE: To study the genetic polymorphisms of /"UDP-glucuronosyltransferase 1F"/(/"UGT1F"/) and the relationship between polymorphisms and susceptibility to /"hepatocellular carcinoma"/ (/"HCC"/). METHODS: The polymorphisms of /"UGT1F"/ of 84 patients with /"HCC"/ and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing. RESULTS: Three new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of /"UGT1F"/ in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant. CONCLUSION: Exons 2-5 of /"UGT1F"/ are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with /"HCC"/. | [
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12181642 | The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population. | Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D require the expression of the nuclear vitamin D receptor (VDR). A three-fold increase in prostate cancer risk associated with the less active vitamin D receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was reported. The role of VDR genotypes in the susceptibility to prostate cancer has not yet been studied in populations of southern Europe. In the present study, we determined VDR TaqI genotypes in Portuguese prostate cancer cases ( n = 163) and controls ( n = 211), a southern European population. When cases were compared with controls, we found an association of VDR T allele with prostate cancer risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02-3.37; P = 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15-3.88; P = 0.015) and in particular associated to risk of prostate cancer onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05-5.29; P = 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe. | The role of /"vitamin D receptor"/ gene polymorphisms in the susceptibility to /"prostate cancer"/ of a southern European population. | Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and /"prostate cancer"/ risk. Antiproliferative effects of vitamin D require the expression of the nuclear /"vitamin D receptor"/ (/"VDR"/). A three-fold increase in /"prostate cancer"/ risk associated with the less active /"vitamin D receptor"/ allele (the T allele from /"VDR"/ TaqI polymorphism at codon 352) was reported. The role of /"VDR"/ genotypes in the susceptibility to /"prostate cancer"/ has not yet been studied in populations of southern Europe. In the present study, we determined /"VDR"/ TaqI genotypes in /"Portuguese prostate cancer"/ cases ( n = 163) and controls ( n = 211), a southern European population. When cases were compared with controls, we found an association of /"VDR"/ T allele with /"prostate cancer"/ risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02-3.37; P = 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15-3.88; P = 0.015) and in particular associated to risk of /"prostate cancer"/ onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05-5.29; P = 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of /"VDR"/ genotypes to /"prostate cancer"/ susceptibility might depend on the population studied and its geographic localization, and that /"VDR"/ genotypes are important in the definition of the genetic risk profile of populations of southern Europe. | [
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12189593 | Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of /"3beta-hydroxysteroid-delta5-desaturase"/. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and /"liver disease"/. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of /"3beta-hydroxysteroid-Delta(5)-desaturase"/ (/"SC5D"/), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the /"SC5D"/ gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | [
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12189593 | Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | Lathosterolosis, a novel multiple-malformation//"mental retardation syndrome"/ due to deficiency of /"3beta-hydroxysteroid-delta5-desaturase"/. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, /"mental retardation"/, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of /"3beta-hydroxysteroid-Delta(5)-desaturase"/ (/"SC5D"/), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the /"SC5D"/ gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | [
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12189593 | Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | /"Lathosterolosis"/, a novel multiple-malformation/mental retardation syndrome due to deficiency of /"3beta-hydroxysteroid-delta5-desaturase"/. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of /"3beta-hydroxysteroid-Delta(5)-desaturase"/ (/"SC5D"/), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the /"SC5D"/ gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | [
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12189593 | Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | /"Lathosterolosis"/, a novel multiple-malformation/mental retardation syndrome due to deficiency of /"3beta-hydroxysteroid-delta5-desaturase"/. | We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of /"3beta-hydroxysteroid-Delta(5)-desaturase"/ (/"SC5D"/), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the /"SC5D"/ gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. | [
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12200750 | The effect of age, body mass index, and fasting triglyceride level on postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects with non-insulin-dependent diabetes mellitus. | The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting triglyceride (TG) status, and glycemic status on postprandial lipemia. Apo E genotyping was performed in consecutive NIDDM hospitalized patients in order to recruite size-adjusted groups of each apo E genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl palmitate (RP) measured. Fasting TG level correlated with the TG area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial TG concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x apo E interaction on postprandial TG (P <.01), since the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In addition, a fasting TG x apo E interaction on postprandial TG was shown (P <.01), and the correlation between fasting TG and TG AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial TG observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between apo E polymorphism and aging, fasting TG level and BMI that may be important for analyzing postprandial TG clearance in NIDDM. | The effect of age, body mass index, and fasting triglyceride level on postprandial lipemia is dependent on /"apolipoprotein E"/ polymorphism in subjects with /"non-insulin-dependent diabetes mellitus"/. | The aim of this study was to evaluate in /"non-insulin-dependent diabetes mellitus"/ (/"NIDDM"/) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting triglyceride (TG) status, and glycemic status on postprandial lipemia. /"Apo E"/ genotyping was performed in consecutive /"NIDDM"/ hospitalized patients in order to recruite size-adjusted groups of each /"apo E"/ genotype. In 57 /"NIDDM"/ including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl palmitate (RP) measured. Fasting TG level correlated with the TG area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial TG concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x /"apo E"/ interaction on postprandial TG (P <.01), since the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In addition, a fasting TG x /"apo E"/ interaction on postprandial TG was shown (P <.01), and the correlation between fasting TG and TG AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial TG observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between /"apo E"/ polymorphism and aging, fasting TG level and BMI that may be important for analyzing postprandial TG clearance in /"NIDDM"/. | [
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12200750 | The effect of age, body mass index, and fasting triglyceride level on postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects with non-insulin-dependent diabetes mellitus. | The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting triglyceride (TG) status, and glycemic status on postprandial lipemia. Apo E genotyping was performed in consecutive NIDDM hospitalized patients in order to recruite size-adjusted groups of each apo E genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl palmitate (RP) measured. Fasting TG level correlated with the TG area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial TG concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x apo E interaction on postprandial TG (P <.01), since the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In addition, a fasting TG x apo E interaction on postprandial TG was shown (P <.01), and the correlation between fasting TG and TG AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial TG observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between apo E polymorphism and aging, fasting TG level and BMI that may be important for analyzing postprandial TG clearance in NIDDM. | The effect of age, body mass index, and fasting /"triglyceride"/ level on postprandial lipemia is dependent on /"apolipoprotein E"/ polymorphism in subjects with non-insulin-dependent diabetes mellitus. | The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting /"triglyceride"/ (/"TG"/) status, and glycemic status on postprandial lipemia. /"Apo E"/ genotyping was performed in consecutive NIDDM hospitalized patients in order to recruite size-adjusted groups of each /"apo E"/ genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and /"TG"/ and retinyl palmitate (RP) measured. Fasting /"TG"/ level correlated with the /"TG"/ area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial /"TG"/ concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x /"apo E"/ interaction on postprandial /"TG"/ (P <.01), since the unfavorable effect of E2 and E4 allele on /"TG"/ AUIC was unmasked by aging. In addition, a fasting /"TG"/ x /"apo E"/ interaction on postprandial /"TG"/ was shown (P <.01), and the correlation between fasting /"TG"/ and /"TG"/ AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial /"TG"/ observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between /"apo E"/ polymorphism and aging, fasting /"TG"/ level and BMI that may be important for analyzing postprandial /"TG"/ clearance in NIDDM. | [
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12209087 | Association of IFNG gene polymorphism with asthma in the Indian population. | Epidemiologic studies in India show that the prevalence of asthma is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the IFNG locus on 12q21 as a candidate gene for asthma on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with asthma and total serum IgE levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with asthma, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the IFNG gene was significantly associated with total serum IgE levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with asthma from the Indian subcontinent. | Association of /"IFNG"/ gene polymorphism with /"asthma"/ in the Indian population. | Epidemiologic studies in India show that the prevalence of /"asthma"/ is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the /"IFNG"/ locus on 12q21 as a candidate gene for /"asthma"/ on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with /"asthma"/ and total serum IgE levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with /"asthma"/, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the /"IFNG"/ gene was significantly associated with total serum IgE levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with /"asthma"/ from the Indian subcontinent. | [
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12209087 | Association of IFNG gene polymorphism with asthma in the Indian population. | Epidemiologic studies in India show that the prevalence of asthma is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the IFNG locus on 12q21 as a candidate gene for asthma on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with asthma and total serum IgE levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with asthma, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the IFNG gene was significantly associated with total serum IgE levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with asthma from the Indian subcontinent. | Association of IFNG gene polymorphism with /"asthma"/ in the Indian population. | Epidemiologic studies in India show that the prevalence of /"asthma"/ is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the IFNG locus on 12q21 as a candidate gene for /"asthma"/ on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with /"asthma"/ and total serum /"IgE"/ levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with /"asthma"/, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the IFNG gene was significantly associated with total serum /"IgE"/ levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with /"asthma"/ from the Indian subcontinent. | [
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12220434 | Genotyping of Israeli infertile men with idiopathic oligozoospermia. | Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal androgen receptor (AR) structure or function has also been implicated in male infertility. To assess the contribution of these genetic defects to male infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the AR-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the AR-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine AR-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to male infertility in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our infertile population than in fertile men. | Genotyping of Israeli infertile men with idiopathic oligozoospermia. | Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal /"androgen receptor"/ (/"AR"/) structure or function has also been implicated in /"male infertility"/. To assess the contribution of these genetic defects to /"male infertility"/, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the /"AR"/-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the /"AR"/-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine /"AR"/-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to /"male infertility"/ in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our infertile population than in fertile men. | [
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12220434 | Genotyping of Israeli infertile men with idiopathic oligozoospermia. | Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal androgen receptor (AR) structure or function has also been implicated in male infertility. To assess the contribution of these genetic defects to male infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the AR-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the AR-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine AR-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to male infertility in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our infertile population than in fertile men. | Genotyping of Israeli /"infertile"/ men with idiopathic oligozoospermia. | Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal /"androgen receptor"/ (/"AR"/) structure or function has also been implicated in male infertility. To assess the contribution of these genetic defects to male infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the /"AR"/-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the /"AR"/-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine /"AR"/-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in /"infertile"/ men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to male infertility in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our /"infertile"/ population than in fertile men. | [
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12297989 | Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH. | Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5p15. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition. | Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein /"ANKH"/. | Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5p15. We have identified a mutation in the /"ANKH"/ gene that segregates with the disease in a family with this condition. /"ANKH"/ encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of /"ANKH"/ causes elevated extracellular PPi levels, predisposing to /"CPPD crystal deposition"/. | [
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"entity_id": "C563162",
"entity_type": "Disease",
"text_name": "CPPD crystal deposition"
} | Yes |
12297989 | Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH. | Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5p15. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition. | Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein /"ANKH"/. | Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) /"chondrocalcinosis"/ has previously been mapped to chromosome 5p15. We have identified a mutation in the /"ANKH"/ gene that segregates with the disease in a family with this condition. /"ANKH"/ encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of /"ANKH"/ causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition. | [
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} | No |
12325071 | Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. | X-linked Charcot-Marie-Tooth disease (CMTX) is a hereditary demyelinating neuropathy caused by mutations in the connexin 32 (Cx32) gene. Cx32 is widely expressed in brain and peripheral nerve, yet clinical manifestations of CMTX mainly arise from peripheral neuropathy. We have evaluated two male patients with CMTX who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in demyelination or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that CMTX patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. Cx32 mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress. | Transient central nervous system white matter abnormality in /"X-linked Charcot-Marie-Tooth disease"/. | /"X-linked Charcot-Marie-Tooth disease"/ (/"CMTX"/TX"/) is a hereditary demyelinating neuropathy caused by mutations in the /"connexin 32"/ (/"Cx32"/) gene. /"Cx32"/ is widely expressed in brain and peripheral nerve, yet clinical manifestations of /"CMTX"/TX"/ mainly arise from peripheral neuropathy. We have evaluated two male patients with /"CMTX"/TX"/ who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in demyelination or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that /"CMTX"/TX"/ patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. /"Cx32"/ mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress. | [
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} | {
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"text_name": "X-linked Charcot-Marie-Tooth disease"
} | Yes |
12325071 | Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. | X-linked Charcot-Marie-Tooth disease (CMTX) is a hereditary demyelinating neuropathy caused by mutations in the connexin 32 (Cx32) gene. Cx32 is widely expressed in brain and peripheral nerve, yet clinical manifestations of CMTX mainly arise from peripheral neuropathy. We have evaluated two male patients with CMTX who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in demyelination or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that CMTX patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. Cx32 mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress. | Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. | X-linked Charcot-Marie-Tooth disease (/"CMTX"/) is a hereditary demyelinating neuropathy caused by mutations in the /"connexin 32"/ (/"Cx32"/) gene. /"Cx32"/ is widely expressed in brain and peripheral nerve, yet clinical manifestations of /"CMTX"/ mainly arise from peripheral neuropathy. We have evaluated two male patients with /"CMTX"/ who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in /"demyelination"/ or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that /"CMTX"/ patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. /"Cx32"/ mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress. | [
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"text_name": "weakness"
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"entity_id": "2705",
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"text_name": "Cx32"
}
] | {
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"end_idx": "240",
"entity_id": "2705",
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"text_name": "Cx32"
} | {
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"end_idx": "904",
"entity_id": "D003711",
"entity_type": "Disease",
"text_name": "demyelination"
} | No |
12355549 | Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study. | N-acetyltransferase-1 (NAT1) and N-acetyltransferase-2 (NAT2) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce prostate tumors in the rat. We investigated the association of genetic polymorphisms in NAT1 and NAT2, alone and in combination, with human prostate cancer. Incident prostate cancer cases and controls in a hospital-based case-control study were frequency-matched for age, race, and referral pattern. The frequency of slow acetylator NAT1 genotypes (NAT1*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other NAT1 genotypes the putative rapid acetylator NAT1 genotype (NAT1*10) was significantly higher in prostate cancer cases than controls (OR, 2.17; 95% CI, 1.08-4.33; P = 0.03). Combinations of NAT1*10 with NAT2 slow acetylator genotypes (OR, 5.08; 95% CI, 1.56-16.5; P = 0.008) or with NAT2 very slow (homozygous NAT2*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55-15.4; P = 0.016) further increased prostate cancer risk. The results of this small pilot study suggest increased susceptibility to prostate cancer for subjects with combinations of NAT1*10 and slow (particularly very slow) NAT2 acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations. | Association of /"prostate cancer"/ with rapid N-acetyltransferase 1 (/"NAT1"/*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study. | N-acetyltransferase-1 (NAT1) and N-acetyltransferase-2 (/"NAT2"/) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce /"prostate tumors"/ in the rat. We investigated the association of genetic polymorphisms in /"NAT1"/ and NAT2, alone and in combination, with human /"prostate cancer"/. Incident /"prostate cancer"/ cases and controls in a hospital-based case-control study were frequency-matched for age, race, and referral pattern. The frequency of slow acetylator /"NAT1"/ genotypes (/"NAT1"/*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other /"NAT1"/ genotypes the putative rapid acetylator /"NAT1"/ genotype (/"NAT1"/*10) was significantly higher in /"prostate cancer"/ cases than controls (OR, 2.17; 95% CI, 1.08-4.33; P = 0.03). Combinations of /"NAT1"/*10 with NAT2 slow acetylator genotypes (OR, 5.08; 95% CI, 1.56-16.5; P = 0.008) or with NAT2 very slow (homozygous NAT2*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55-15.4; P = 0.016) further /"increased prostate cancer"/ risk. The results of this small pilot study suggest increased susceptibility to /"prostate cancer"/ for subjects with combinations of /"NAT1"/*10 and slow (particularly very slow) NAT2 acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations. | [
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} | {
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"entity_id": "D011471",
"entity_type": "Disease",
"text_name": "increased prostate cancer"
} | Yes |
12355549 | Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study. | N-acetyltransferase-1 (NAT1) and N-acetyltransferase-2 (NAT2) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce prostate tumors in the rat. We investigated the association of genetic polymorphisms in NAT1 and NAT2, alone and in combination, with human prostate cancer. Incident prostate cancer cases and controls in a hospital-based case-control study were frequency-matched for age, race, and referral pattern. The frequency of slow acetylator NAT1 genotypes (NAT1*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other NAT1 genotypes the putative rapid acetylator NAT1 genotype (NAT1*10) was significantly higher in prostate cancer cases than controls (OR, 2.17; 95% CI, 1.08-4.33; P = 0.03). Combinations of NAT1*10 with NAT2 slow acetylator genotypes (OR, 5.08; 95% CI, 1.56-16.5; P = 0.008) or with NAT2 very slow (homozygous NAT2*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55-15.4; P = 0.016) further increased prostate cancer risk. The results of this small pilot study suggest increased susceptibility to prostate cancer for subjects with combinations of NAT1*10 and slow (particularly very slow) NAT2 acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations. | Association of /"prostate cancer"/ with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow /"N-acetyltransferase 2"/ acetylator genotypes in a pilot case-control study. | N-acetyltransferase-1 (/"NAT1"/) and N-acetyltransferase-2 (NAT2) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce /"prostate tumors"/ in the rat. We investigated the association of genetic polymorphisms in NAT1 and /"NAT2"/, alone and in combination, with human /"prostate cancer"/. Incident /"prostate cancer"/ cases and controls in a hospital-based case-control study were frequency-matched for age, race, and referral pattern. The frequency of slow acetylator NAT1 genotypes (NAT1*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other NAT1 genotypes the putative rapid acetylator NAT1 genotype (NAT1*10) was significantly higher in /"prostate cancer"/ cases than controls (OR, 2.17; 95% CI, 1.08-4.33; P = 0.03). Combinations of NAT1*10 with /"NAT2"/ slow acetylator genotypes (OR, 5.08; 95% CI, 1.56-16.5; P = 0.008) or with /"NAT2"/ very slow (homozygous /"NAT2"/*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55-15.4; P = 0.016) further /"increased prostate cancer"/ risk. The results of this small pilot study suggest increased susceptibility to /"prostate cancer"/ for subjects with combinations of NAT1*10 and slow (particularly very slow) /"NAT2"/ acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations. | [
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} | Yes |
12358323 | BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. | This study investigated whether patients developing pulmonary arterial hypertension (PAH) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene, as reported in primary pulmonary hypertension. BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls. The PAH patients also underwent cardiac catheterisation and body mass determinations. Three BMPR2 mutations predicting changes in the primary structure of the BMPR-II protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No BMPR2 mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients, a difference that was statistically significant when the two sisters were included in the analysis. In conclusion, the present authors have detected bone morphogenetic protein receptor 2 mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe pulmonary arterial hypertension. | /"BMPR2"/ germline mutations in /"pulmonary hypertension"/ associated with fenfluramine derivatives. | This study investigated whether patients developing /"pulmonary arterial hypertension"/ (/"PAH"/) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the /"bone morphogenetic protein receptor 2"/ (/"BMPR2"/) gene, as reported in /"primary pulmonary hypertension"/. /"BMPR2"/ was examined for mutations in 33 unrelated patients with sporadic /"PAH"/, and in two sisters with /"PAH"/, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls. The /"PAH"/ patients also underwent cardiac catheterisation and body mass determinations. Three /"BMPR2"/ mutations predicting changes in the primary structure of the /"BMPR-II"/ protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No /"BMPR2"/ mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients, a difference that was statistically significant when the two sisters were included in the analysis. In conclusion, the present authors have detected /"bone morphogenetic protein receptor 2"/ mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe /"pulmonary arterial hypertension"/. | [
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12373604 | BRCA2 gene mutations in families with aggregations of breast and stomach cancers. | Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the E-cadherin gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in BRCA2 gene mutation carriers. We analysed by direct sequencing the BRCA2 gene in 29 breast cancer patients derived from 29 families with an aggregation of at least one female breast cancer diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants - potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that BRCA2 gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact. | /"BRCA2"/ gene mutations in families with aggregations of /"breast and stomach cancers"/. | Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the E-cadherin gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in /"BRCA2"/ gene mutation carriers. We analysed by direct sequencing the /"BRCA2"/ gene in 29 /"breast cancer"/ patients derived from 29 families with an aggregation of at least one female /"breast cancer"/ diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants - potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that /"BRCA2"/ gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact. | [
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12373604 | BRCA2 gene mutations in families with aggregations of breast and stomach cancers. | Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the E-cadherin gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in BRCA2 gene mutation carriers. We analysed by direct sequencing the BRCA2 gene in 29 breast cancer patients derived from 29 families with an aggregation of at least one female breast cancer diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants - potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that BRCA2 gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact. | BRCA2 gene mutations in families with aggregations of /"breast and stomach cancers"/. | Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the /"E-cadherin"/ gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in BRCA2 gene mutation carriers. We analysed by direct sequencing the BRCA2 gene in 29 /"breast cancer"/ patients derived from 29 families with an aggregation of at least one female /"breast cancer"/ diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants - potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that BRCA2 gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact. | [
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12377406 | Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk. | The 8p22 through p23 region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk. | Germline sequence variants of the /"LZTS1"/ gene are associated with /"prostate cancer"/ risk. | The 8p22 through p23 region has been identified as a potential site for genes associated with /"prostate cancer"/. The gene /"LZTS1"/ has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates /"LZTS1"/ function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of /"LZTS1"/ was performed in a screening panel consisting of sporadic and /"hereditary prostate cancer"/ (/"HPC"/) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 /"HPC"/ probands, 245 /"sporadic prostate cancer"/ cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with /"prostate cancer"/ (P < or = 0.04). These results add evidence supporting a role of /"LZTS1"/ in /"prostate cancer"/ risk. | [
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12377406 | Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk. | The 8p22 through p23 region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk. | Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk. | The 8p22 through /"p23"/ region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through /"p23"/ region and identified as a potential /"tumor"/ suppressor based on loss of heterozygosity studies using primary /"esophageal tumors"/. Sequence analysis of mRNA from various /"tumors"/ has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk. | [
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12378512 | Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of p53 mutations. | Abnormalities of the ARF-/"p53"/ pathway in primary /"angiosarcomas of the liver"/. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and /"p53"/ pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of /"angiosarcoma of the liver"/. Alterations of p14(ARF), p16(INKa), and /"p53"/ in primary /"liver angiosarcoma"/ from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of /"p53"/ mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or /"p53"/ as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in /"angiosarcoma of the liver"/ and occurs independently of /"p53"/ mutations. | [
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12378512 | Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of p53 mutations. | Abnormalities of the ARF-p53 pathway in primary /"angiosarcomas of the liver"/. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, /"p16"/(INKa) and /"p14"/(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of /"angiosarcoma of the liver"/. Alterations of /"p14"/(ARF), /"p16"/(INKa), and p53 in primary /"liver angiosarcoma"/ from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of /"p14"/(ARF) was found in 5 of 19 cases (26%), and /"p16"/(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated /"p14"/(ARF) appeared in the context of a methylated /"p16"/(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at /"p14"/(ARF). /"p14"/(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in /"angiosarcoma of the liver"/ and occurs independently of p53 mutations. | [
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12378512 | Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of p53 mutations. | Abnormalities of the ARF-/"p53"/ pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and /"p53"/ pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and /"p53"/ in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One /"tumor"/ (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of /"p53"/ mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or /"p53"/ as were not established independent prognostic factors in these /"tumors"/. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of /"p53"/ mutations. | [
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} | No |
12378512 | Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of p53 mutations. | Abnormalities of the ARF-/"p53"/ pathway in primary angiosarcomas of the liver. | The INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and /"p53"/ pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and /"p53"/ in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 /"angiosarcomas"/ from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 /"angiosarcomas"/ methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of /"p53"/ mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or /"p53"/ as were not established independent prognostic factors in these tumors. In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of /"p53"/ mutations. | [
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} | No |
12394840 | Apolipoprotein E gene polymorphism alters lipids before pancreas transplantation. | BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is apolipoprotein E (Apo E) genotype. Apo E polymorphism, particularly E2 and E4 alleles, increases the risk of dyslipidemia. Apo E2 has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of Apo E genotype on dyslipidemia before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an Apo E4 allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an Apo E2 allele had no significant effect on lipids before or after PTX. Thus, Apo E4 has a larger impact than Apo E2 on fasting-lipid profile in PTX candidates, and Apo E gene polymorphism does not worsen lipid dyslipidemia after PTX, despite introduction of immunosuppressant medications known to cause dyslipidemia. | /"Apolipoprotein E"/ gene polymorphism alters lipids before pancreas transplantation. | BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new /"hyperlipidemia"/ despite PTX. One factor that may influence the lipid profile is /"apolipoprotein E"/ (/"Apo E"/) genotype. /"Apo E"/ polymorphism, particularly E2 and E4 alleles, increases the risk of dyslipidemia. /"Apo E2"/ has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of /"Apo E"/ genotype on dyslipidemia before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an /"Apo E4"/ allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an /"Apo E2"/ allele had no significant effect on lipids before or after PTX. Thus, /"Apo E4"/ has a larger impact than /"Apo E2"/ on fasting-lipid profile in PTX candidates, and /"Apo E"/ gene polymorphism does not worsen lipid dyslipidemia after PTX, despite introduction of immunosuppressant medications known to cause dyslipidemia. | [
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} | Yes |
12394840 | Apolipoprotein E gene polymorphism alters lipids before pancreas transplantation. | BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is apolipoprotein E (Apo E) genotype. Apo E polymorphism, particularly E2 and E4 alleles, increases the risk of dyslipidemia. Apo E2 has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of Apo E genotype on dyslipidemia before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an Apo E4 allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an Apo E2 allele had no significant effect on lipids before or after PTX. Thus, Apo E4 has a larger impact than Apo E2 on fasting-lipid profile in PTX candidates, and Apo E gene polymorphism does not worsen lipid dyslipidemia after PTX, despite introduction of immunosuppressant medications known to cause dyslipidemia. | /"Apolipoprotein E"/ gene polymorphism alters lipids before pancreas transplantation. | BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is /"apolipoprotein E"/ (/"Apo E"/) genotype. /"Apo E"/ polymorphism, particularly E2 and E4 alleles, increases the risk of /"dyslipidemia"/. /"Apo E2"/ has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of /"Apo E"/ genotype on /"dyslipidemia"/ before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an /"Apo E4"/ allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an /"Apo E2"/ allele had no significant effect on lipids before or after PTX. Thus, /"Apo E4"/ has a larger impact than /"Apo E2"/ on fasting-lipid profile in PTX candidates, and /"Apo E"/ gene polymorphism does not worsen /"lipid dyslipidemia"/ after PTX, despite introduction of immunosuppressant medications known to cause /"dyslipidemia"/. | [
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12409629 | Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: comparison among CETP/TaqIB genotype subgroups. | We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments. | Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary /"hypercholesterolemia"/: comparison among /"CETP"//TaqIB genotype subgroups. | We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (/"CETP"/) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the /"CETP"/ gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma /"CETP"/ were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma /"CETP"/ activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma /"CETP"/ were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma /"CETP"/ in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma /"CETP"/ compared to the other genotypes. The genetic variation in the /"CETP"/ gene may be one important factor in designing better treatments. | [
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] | {
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} | {
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} | Yes |
12409629 | Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: comparison among CETP/TaqIB genotype subgroups. | We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments. | Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: comparison among /"CETP"//TaqIB genotype subgroups. | We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (/"CETP"/) in 30 /"hypercholesterolemic"/ patients. Patients were divided into three groups according to TaqIB polymorphism of the /"CETP"/ gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma /"CETP"/ were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma /"CETP"/ activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma /"CETP"/ were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma /"CETP"/ in /"hypercholesterolemic"/ patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma /"CETP"/ compared to the other genotypes. The genetic variation in the /"CETP"/ gene may be one important factor in designing better treatments. | [
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12476417 | [The G894T mutation of the endothelial nitric oxide synthase gene is associated with coronary atherosclerotic heart disease in Chinese]. | OBJECTIVE: To investigate the association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with coronary atherosclerotic heart disease (CHD) in Chinese Han nationality. METHODS: For 106 patients with CHD and 108 unrelated health individuals, the G894T mutation at exon 7 of the endothelial nitric oxide synthase gene was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: (1) Among the normal subjects of Chinese Han nationality, the frequencies of the eNOS/GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. The G and T allele frequencies were 0.9537 and 0.0463. (2) The authors assumed the effects of the T allele to be dominant (GT and TT combined vs GG). The GT+TT genotype frequencies in CHD and myocardial infarction (MI) subgroup were 0.2219 and 0.2387, respectively. The frequencies of eNOS/GT+TT genotypes in CHD patients, as well as MI subgroup were significantly higher than that of the normal subjects (P<0.05), respectively. The frequencies of T allele in CHD, MI subgroup were significantly higher than that in the normal subjects (P<0.01), respectively. (3) This mutation was not related to the number of affected vessels in the 58 patients who had angiographically documented artery narrowing (P>0.05). CONCLUSION: The G894T mutation of the endothelial nitric oxide synthase gene may be a marker for genetical predisposition of CHD in Chinese Han population. | [The G894T mutation of the /"endothelial nitric oxide synthase"/ gene is associated with /"coronary atherosclerotic heart disease"/ in Chinese]. | OBJECTIVE: To investigate the association of the /"endothelial nitric oxide synthase"/ (eNOS) gene polymorphism with /"coronary atherosclerotic heart disease"/ (/"CHD"/) in Chinese Han nationality. METHODS: For 106 patients with /"CHD"/ and 108 unrelated health individuals, the G894T mutation at exon 7 of the /"endothelial nitric oxide synthase"/ gene was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: (1) Among the normal subjects of Chinese Han nationality, the frequencies of the eNOS/GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. The G and T allele frequencies were 0.9537 and 0.0463. (2) The authors assumed the effects of the T allele to be dominant (GT and TT combined vs GG). The GT+TT genotype frequencies in /"CHD"/ and myocardial infarction (MI) subgroup were 0.2219 and 0.2387, respectively. The frequencies of eNOS/GT+TT genotypes in /"CHD"/ patients, as well as MI subgroup were significantly higher than that of the normal subjects (P<0.05), respectively. The frequencies of T allele in /"CHD"/, MI subgroup were significantly higher than that in the normal subjects (P<0.01), respectively. (3) This mutation was not related to the number of affected vessels in the 58 patients who had angiographically documented artery narrowing (P>0.05). CONCLUSION: The G894T mutation of the /"endothelial nitric oxide synthase"/ gene may be a marker for genetical predisposition of /"CHD"/ in Chinese Han population. | [
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} | Yes |
12476417 | [The G894T mutation of the endothelial nitric oxide synthase gene is associated with coronary atherosclerotic heart disease in Chinese]. | OBJECTIVE: To investigate the association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with coronary atherosclerotic heart disease (CHD) in Chinese Han nationality. METHODS: For 106 patients with CHD and 108 unrelated health individuals, the G894T mutation at exon 7 of the endothelial nitric oxide synthase gene was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: (1) Among the normal subjects of Chinese Han nationality, the frequencies of the eNOS/GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. The G and T allele frequencies were 0.9537 and 0.0463. (2) The authors assumed the effects of the T allele to be dominant (GT and TT combined vs GG). The GT+TT genotype frequencies in CHD and myocardial infarction (MI) subgroup were 0.2219 and 0.2387, respectively. The frequencies of eNOS/GT+TT genotypes in CHD patients, as well as MI subgroup were significantly higher than that of the normal subjects (P<0.05), respectively. The frequencies of T allele in CHD, MI subgroup were significantly higher than that in the normal subjects (P<0.01), respectively. (3) This mutation was not related to the number of affected vessels in the 58 patients who had angiographically documented artery narrowing (P>0.05). CONCLUSION: The G894T mutation of the endothelial nitric oxide synthase gene may be a marker for genetical predisposition of CHD in Chinese Han population. | [The G894T mutation of the /"endothelial nitric oxide synthase"/ gene is associated with coronary atherosclerotic heart disease in Chinese]. | OBJECTIVE: To investigate the association of the /"endothelial nitric oxide synthase"/ (eNOS) gene polymorphism with coronary atherosclerotic heart disease (CHD) in Chinese Han nationality. METHODS: For 106 patients with CHD and 108 unrelated health individuals, the G894T mutation at exon 7 of the /"endothelial nitric oxide synthase"/ gene was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: (1) Among the normal subjects of Chinese Han nationality, the frequencies of the eNOS/GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. The G and T allele frequencies were 0.9537 and 0.0463. (2) The authors assumed the effects of the T allele to be dominant (GT and TT combined vs GG). The GT+TT genotype frequencies in CHD and /"myocardial infarction"/ (/"MI"/) subgroup were 0.2219 and 0.2387, respectively. The frequencies of eNOS/GT+TT genotypes in CHD patients, as well as /"MI"/ subgroup were significantly higher than that of the normal subjects (P<0.05), respectively. The frequencies of T allele in CHD, /"MI"/ subgroup were significantly higher than that in the normal subjects (P<0.01), respectively. (3) This mutation was not related to the number of affected vessels in the 58 patients who had angiographically documented artery narrowing (P>0.05). CONCLUSION: The G894T mutation of the /"endothelial nitric oxide synthase"/ gene may be a marker for genetical predisposition of CHD in Chinese Han population. | [
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12484521 | Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of hypertension in a Chinese Han population. | Accumulating data support an association between hypertension and impaired fibrinolytic potential abnormalities in endogenous fibrinolysis. The present study examined whether there was an association between essential hypertension and either a polymorphism in the gene coding for t-PA or the plasma concentration of t-PA antigen. Chinese hypertensive subjects (n = 126) and normotensive controls (n = 102; sex- and age-matched with hypertensives) were recruited from among the outpatients of FuWai Hospital. The distributions of the II, ID, and DD genotypes of the t-PA gene in hypertensive patients (0.15, 0.49, 0.36) were similar to those in control subjects (0.11, 0.51, 0.38; p = 0.626). No significant difference in overall allele frequencies was found between the hypertension and control groups (p = 0.656). The allelic frequencies were in Hardy-Weinberg equilibrium. There was no evidence of an association between the level of t-PA antigen and risk of hypertension. Thus, in this case control study, neither the presence of the insertion allele of the Alu-repeat polymorphism of the t-PA nor the level of t-PA antigen were associated with the risk of essential hypertension. | Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of /"hypertension"/ in a Chinese Han population. | Accumulating data support an association between /"hypertension"/ and impaired fibrinolytic potential abnormalities in endogenous fibrinolysis. The present study examined whether there was an association between essential /"hypertension"/ and either a polymorphism in the gene coding for /"t-PA"/ or the plasma concentration of /"t-PA"/ antigen. Chinese /"hypertensive"/ subjects (n = 126) and normotensive controls (n = 102; sex- and age-matched with /"hypertensives"/) were recruited from among the outpatients of FuWai Hospital. The distributions of the II, ID, and DD genotypes of the /"t-PA"/ gene in /"hypertensive"/ patients (0.15, 0.49, 0.36) were similar to those in control subjects (0.11, 0.51, 0.38; p = 0.626). No significant difference in overall allele frequencies was found between the /"hypertension"/ and control groups (p = 0.656). The allelic frequencies were in Hardy-Weinberg equilibrium. There was no evidence of an association between the level of /"t-PA"/ antigen and risk of /"hypertension"/. Thus, in this case control study, neither the presence of the insertion allele of the Alu-repeat polymorphism of the /"t-PA"/ nor the level of /"t-PA"/ antigen were associated with the risk of essential /"hypertension"/. | [
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12492589 | Fcgamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura. | Fcgamma receptor-mediated destruction of autoantibody-sensitized platelets is central to the immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic variants exist among the random population for some Fcgamma receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcgamma receptor single nucleotide polymorphisms, FcgammaRIIa-131 arginine (R) versus histidine (H) and FcgammaRIIIa-158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood ITP. The genotype frequencies were compared with those of 130 healthy control subjects. Chi-square analysis was used to determine whether the allelic frequencies of the high-affinity receptor variants were associated with childhood ITP. Both the FcgammaRIIa-131H and the FcgammaRIIIa-158V were significantly over-represented in children with ITP versus the control subjects (P-values 0.03). The same statistical difference was noted with the combined FcgammaRIIa-131H and FcgammaRIIIa-158V allelic gene frequencies. There was no statistical difference between children who later developed chronic ITP compared with children with acute ITP, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcgamma receptor-mediated cell clearance in childhood ITP. | /"Fcgamma receptor IIa"/ and IIIa polymorphisms in childhood /"immune thrombocytopenic purpura"/. | Fcgamma receptor-mediated destruction of autoantibody-sensitized platelets is central to the immune pathophysiology of childhood /"immune thrombocytopenic purpura"/ (/"ITP"/). Allelic variants exist among the random population for some Fcgamma receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcgamma receptor single nucleotide polymorphisms, FcgammaRIIa-131 arginine (R) versus histidine (H) and FcgammaRIIIa-158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood /"ITP"/. The genotype frequencies were compared with those of 130 healthy control subjects. Chi-square analysis was used to determine whether the allelic frequencies of the high-affinity receptor variants were associated with childhood /"ITP"/. Both the FcgammaRIIa-131H and the FcgammaRIIIa-158V were significantly over-represented in children with /"ITP"/ versus the control subjects (P-values 0.03). The same statistical difference was noted with the combined FcgammaRIIa-131H and FcgammaRIIIa-158V allelic gene frequencies. There was no statistical difference between children who later developed chronic /"ITP"/ compared with children with /"acute ITP"/, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcgamma receptor-mediated cell clearance in childhood /"ITP"/. | [
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},
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} | Yes |
12492589 | Fcgamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura. | Fcgamma receptor-mediated destruction of autoantibody-sensitized platelets is central to the immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic variants exist among the random population for some Fcgamma receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcgamma receptor single nucleotide polymorphisms, FcgammaRIIa-131 arginine (R) versus histidine (H) and FcgammaRIIIa-158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood ITP. The genotype frequencies were compared with those of 130 healthy control subjects. Chi-square analysis was used to determine whether the allelic frequencies of the high-affinity receptor variants were associated with childhood ITP. Both the FcgammaRIIa-131H and the FcgammaRIIIa-158V were significantly over-represented in children with ITP versus the control subjects (P-values 0.03). The same statistical difference was noted with the combined FcgammaRIIa-131H and FcgammaRIIIa-158V allelic gene frequencies. There was no statistical difference between children who later developed chronic ITP compared with children with acute ITP, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcgamma receptor-mediated cell clearance in childhood ITP. | Fcgamma receptor IIa and IIIa polymorphisms in childhood /"immune thrombocytopenic purpura"/. | Fcgamma receptor-mediated destruction of autoantibody-sensitized platelets is central to the immune pathophysiology of childhood /"immune thrombocytopenic purpura"/ (/"ITP"/). Allelic variants exist among the random population for some Fcgamma receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcgamma receptor single nucleotide polymorphisms, FcgammaRIIa-131 arginine (R) versus histidine (H) and /"FcgammaRIIIa"/-158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood /"ITP"/. The genotype frequencies were compared with those of 130 healthy control subjects. Chi-square analysis was used to determine whether the allelic frequencies of the high-affinity receptor variants were associated with childhood /"ITP"/. Both the FcgammaRIIa-131H and the /"FcgammaRIIIa"/-158V were significantly over-represented in children with /"ITP"/ versus the control subjects (P-values 0.03). The same statistical difference was noted with the combined FcgammaRIIa-131H and /"FcgammaRIIIa"/-158V allelic gene frequencies. There was no statistical difference between children who later developed chronic /"ITP"/ compared with children with /"acute ITP"/, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcgamma receptor-mediated cell clearance in childhood /"ITP"/. | [
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12498973 | Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's disease. | Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of AD (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between ICAM-1 E/K gene polymorphism and AD, suggesting that polymorphisms of the ICAM-1 gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of neuro-degenerative diseases. | /"Intercellular adhesion molecule-1"/ K469E gene polymorphism and /"Alzheimer's disease"/. | Inflammatory processes are considered important in the pathogenesis of /"Alzheimer's disease"/ (/"AD"/). /"Intercellular adhesion molecule-1"/ (/"ICAM-1"/) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of /"AD"/ patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the /"ICAM-1"/ gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the /"ICAM-1"/ gene in 98 patients affected by sporadic /"AD"/ and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in /"AD"/ patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of /"AD"/ (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between /"ICAM-1"/ E/K gene polymorphism and /"AD"/, suggesting that polymorphisms of the /"ICAM-1"/ gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of neuro-degenerative diseases. | [
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} | {
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"entity_id": "D000544",
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"text_name": "Alzheimer's disease"
} | Yes |
12498973 | Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's disease. | Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of AD (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between ICAM-1 E/K gene polymorphism and AD, suggesting that polymorphisms of the ICAM-1 gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of neuro-degenerative diseases. | /"Intercellular adhesion molecule-1"/ K469E gene polymorphism and Alzheimer's disease. | Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). /"Intercellular adhesion molecule-1"/ (/"ICAM-1"/) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the /"ICAM-1"/ gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the /"ICAM-1"/ gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of AD (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between /"ICAM-1"/ E/K gene polymorphism and AD, suggesting that polymorphisms of the /"ICAM-1"/ gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of /"neuro-degenerative diseases"/. | [
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12502508 | Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. | We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy. | Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental /"diabetic neuropathy"/. | We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. /"Experimental diabetic neuropathy"/ was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. /"Caspase-3"/ labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy. | [
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} | Yes |
12502508 | Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. | We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy. | Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. | We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of /"diabetes"/. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. /"Caspase-3"/ labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy. | [
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} | No |
12525557 | CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients. | /"CYP1B1"/ gene analysis in primary /"congenital glaucoma"/ in Indonesian and European patients. | [
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||
12574109 | Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with hypertension in middle-aged men. | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1/PGC-1) is a transcriptional coactivator of nuclear hormone receptors implicated in blood pressure regulation. We therefore ascertained whether the PPARGC1 gene locus is associated with hypertension. We studied associations of 3 polymorphisms in PPARGC1 transcripts with hypertension in 683 middle-aged men and 530 middle-aged women of a cross-sectional Austrian population. Hypertension was defined by average values of systolic or diastolic ambulatory blood pressure readings (taken between 7 AM and 10 PM) above 140 and/or 90 and/or use of antihypertensive medication. Among the 3 polymorphic sites, genotype distributions associated with Gly482Ser differed by hypertension status in men (P=0.0038), but not in women. The less common Ser482 allele was associated with a modest, but significant, reduction in the prevalence of hypertension in men. The distribution of 3 loci haplotypes also differed in men with and without hypertension (P=0.015). Despite its moderate effect, but because of its high frequency (approximately 64%), the more common risk allele contributed to hypertension in 35% (95% CI 16% to 54%) of our male population. These results suggest, but do not prove, that PPARGC1 participates in blood pressure control, and sequence substitutions at its gene locus confer an increased risk of hypertension to a substantial proportion of men. | Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with /"hypertension"/ in middle-aged men. | Peroxisome proliferator-activated receptor-gamma coactivator-1 (/"PPARGC1"///"PGC-1"/) is a transcriptional coactivator of nuclear hormone receptors implicated in blood pressure regulation. We therefore ascertained whether the /"PPARGC1"/ gene locus is associated with /"hypertension"/. We studied associations of 3 polymorphisms in /"PPARGC1"/ transcripts with /"hypertension"/ in 683 middle-aged men and 530 middle-aged women of a cross-sectional Austrian population. /"Hypertension"/ was defined by average values of systolic or diastolic ambulatory blood pressure readings (taken between 7 AM and 10 PM) above 140 and/or 90 and/or use of antihypertensive medication. Among the 3 polymorphic sites, genotype distributions associated with Gly482Ser differed by /"hypertension"/ status in men (P=0.0038), but not in women. The less common Ser482 allele was associated with a modest, but significant, reduction in the prevalence of /"hypertension"/ in men. The distribution of 3 loci haplotypes also differed in men with and without /"hypertension"/ (P=0.015). Despite its moderate effect, but because of its high frequency (approximately 64%), the more common risk allele contributed to /"hypertension"/ in 35% (95% CI 16% to 54%) of our male population. These results suggest, but do not prove, that /"PPARGC1"/ participates in blood pressure control, and sequence substitutions at its gene locus confer an increased risk of /"hypertension"/ to a substantial proportion of men. | [
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12579522 | Pathophysiological role of nitric oxide and adrenomedullin in autism. | Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder. | Pathophysiological role of nitric oxide and /"adrenomedullin"/ in /"autism"/. | Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in /"autism"/. /"Adrenomedullin"/ (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in /"autistic"/ patients and aimed to examine these molecules. Twenty-six /"autistic"/ patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the /"autistic"/ group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating /"autistic"/ patients in earlier periods of life and with subtypes of the disorder. | [
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12579522 | Pathophysiological role of nitric oxide and adrenomedullin in autism. | Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder. | Pathophysiological role of nitric oxide and /"adrenomedullin"/ in autism. | Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, /"depression"/, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. /"Adrenomedullin"/ (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder. | [
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12579739 | [Analysis of rhodopsin and peripherin/RDS genes in Chinese patients with retinitis pigmentosa]. | PURPOSE: To disclose the mutation of rhodopsin and peripherin/RDS genes among Chinese patients with retinitis pigmentosa as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and peripherin/RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with retinitis pigmentosa(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with autosomal recessive retinitis pigmentosa. Mutation of peripherin/RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with retinitis pigmentosa, either autosomal dominant, recessive or sporadic. | [Analysis of rhodopsin and peripherin//"RDS"/ genes in Chinese patients with /"retinitis pigmentosa"/]. | PURPOSE: To disclose the mutation of rhodopsin and peripherin//"RDS"/ genes among Chinese patients with /"retinitis pigmentosa"/ as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and peripherin//"RDS"/ genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with /"retinitis pigmentosa"/(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with /"autosomal recessive retinitis pigmentosa"/. Mutation of peripherin//"RDS"/ gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with /"retinitis pigmentosa"/, either autosomal dominant, recessive or sporadic. | [
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"text_name": "autosomal recessive retinitis pigmentosa"
} | Yes |
12579739 | [Analysis of rhodopsin and peripherin/RDS genes in Chinese patients with retinitis pigmentosa]. | PURPOSE: To disclose the mutation of rhodopsin and peripherin/RDS genes among Chinese patients with retinitis pigmentosa as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and peripherin/RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with retinitis pigmentosa(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with autosomal recessive retinitis pigmentosa. Mutation of peripherin/RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with retinitis pigmentosa, either autosomal dominant, recessive or sporadic. | [Analysis of /"rhodopsin"/ and peripherin/RDS genes in Chinese patients with /"retinitis pigmentosa"/]. | PURPOSE: To disclose the mutation of /"rhodopsin"/ and peripherin/RDS genes among Chinese patients with /"retinitis pigmentosa"/ as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the /"rhodopsin"/ and peripherin/RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the /"rhodopsin"/ gene were found in 3 of the 83 patients with /"retinitis pigmentosa"/(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with /"autosomal recessive retinitis pigmentosa"/. Mutation of peripherin/RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the /"rhodopsin"/ gene is the common cause in Chinese patients with /"retinitis pigmentosa"/, either autosomal dominant, recessive or sporadic. | [
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"entity_type": "Disease",
"text_name": "autosomal recessive retinitis pigmentosa"
} | Yes |
12579739 | [Analysis of rhodopsin and peripherin/RDS genes in Chinese patients with retinitis pigmentosa]. | PURPOSE: To disclose the mutation of rhodopsin and peripherin/RDS genes among Chinese patients with retinitis pigmentosa as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and peripherin/RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with retinitis pigmentosa(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with autosomal recessive retinitis pigmentosa. Mutation of peripherin/RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with retinitis pigmentosa, either autosomal dominant, recessive or sporadic. | [Analysis of rhodopsin and /"peripherin"//RDS genes in Chinese patients with /"retinitis pigmentosa"/]. | PURPOSE: To disclose the mutation of rhodopsin and /"peripherin"//RDS genes among Chinese patients with /"retinitis pigmentosa"/ as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and /"peripherin"//RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with /"retinitis pigmentosa"/(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with /"autosomal recessive retinitis pigmentosa"/. Mutation of /"peripherin"//RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with /"retinitis pigmentosa"/, either autosomal dominant, recessive or sporadic. | [
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"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "autosomal recessive retinitis pigmentosa"
} | No |
12579739 | [Analysis of rhodopsin and peripherin/RDS genes in Chinese patients with retinitis pigmentosa]. | PURPOSE: To disclose the mutation of rhodopsin and peripherin/RDS genes among Chinese patients with retinitis pigmentosa as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and peripherin/RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with retinitis pigmentosa(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with autosomal recessive retinitis pigmentosa. Mutation of peripherin/RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with retinitis pigmentosa, either autosomal dominant, recessive or sporadic. | [Analysis of rhodopsin and /"peripherin"//RDS genes in Chinese patients with /"retinitis pigmentosa"/]. | PURPOSE: To disclose the mutation of rhodopsin and /"peripherin"//RDS genes among Chinese patients with /"retinitis pigmentosa"/ as there was no identified mutation through sequencing reported in Chinese. METHODS: Genomic DNA was prepared from the peripheral lymphocytes. Gene fragments of the rhodopsin and /"peripherin"//RDS genes were amplified by the polymerase chain reaction. The PCR products were analyzed by Heteroduplex-SSCP technique. PCR samples with aberrant migrational bands were identified through direct sequencing or cloning sequencing. RESULTS: Three different mutations in the rhodopsin gene were found in 3 of the 83 patients with /"retinitis pigmentosa"/(Va1104Phe, Lys311Glu, Pro347Leu). Two of the three mutations have not been reported before. One of the two (heterozygous, Va1104Phe) was found in an isolated patient and the other (homozygous, Lys311Glu) in a family with /"autosomal recessive retinitis pigmentosa"/. Mutation of /"peripherin"//RDS gene was not found in the 83 patients. CONCLUSION: Mutation in the rhodopsin gene is the common cause in Chinese patients with /"retinitis pigmentosa"/, either autosomal dominant, recessive or sporadic. | [
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} | {
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"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
} | No |
12582029 | No association between OGG1 Ser326Cys polymorphism and breast cancer risk. | No association between /"OGG1"/ Ser326Cys polymorphism and /"breast cancer"/ risk. | [
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"text_name": "breast cancer"
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"text_name": "OGG1"
}
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} | {
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"entity_id": "D001943",
"entity_type": "Disease",
"text_name": "breast cancer"
} | Yes |
||
12586300 | HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection. | /"HFE"/ mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous /"HFE"/ mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). /"HFE"/ heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to /"HFE"/ wildtypes. By multivariate regression analysis odds ratios for /"liver cirrhosis"/ were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to /"HFE"/ wildtypes. Considering all /"HFE"/ heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for /"HFE"/ mutations should be considered in HCV infection. | [
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}
] | {
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} | {
"begin_idx": "1071",
"end_idx": "1086",
"entity_id": "D008103",
"entity_type": "Disease",
"text_name": "liver cirrhosis"
} | Yes |
12586300 | HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection. | /"HFE"/ mutations and /"chronic hepatitis C"/: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous /"HFE"/ mutations on the course of /"chronic hepatitis C"/ and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). /"HFE"/ heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to /"HFE"/ wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to /"HFE"/ wildtypes. Considering all /"HFE"/ heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for /"HFE"/ mutations should be considered in HCV infection. | [
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12586300 | HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection. | /"HFE"/ mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver /"fibrosis"/ and /"cirrhosis"/. | BACKGROUND/AIMS: The impact of heterozygous /"HFE"/ mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). /"HFE"/ heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and /"fibrosis"/ scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to /"HFE"/ wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to /"HFE"/ wildtypes. Considering all /"HFE"/ heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for /"cirrhosis"/ and 3.1 (CI 1.3-7.3; P<0.009) for /"fibrosis"/ were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver /"fibrosis"/ and /"cirrhosis"/ in HCV infected individuals. Screening for /"HFE"/ mutations should be considered in HCV infection. | [
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"text_name": "fibrosis"
} | No |
12586300 | HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. | BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection. | /"HFE"/ mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver /"fibrosis"/ and /"cirrhosis"/. | BACKGROUND/AIMS: The impact of heterozygous /"HFE"/ mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). /"HFE"/ heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and /"fibrosis"/ scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to /"HFE"/ wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to /"HFE"/ wildtypes. Considering all /"HFE"/ heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for /"cirrhosis"/ and 3.1 (CI 1.3-7.3; P<0.009) for /"fibrosis"/ were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver /"fibrosis"/ and /"cirrhosis"/ in HCV infected individuals. Screening for /"HFE"/ mutations should be considered in HCV infection. | [
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12618866 | Enhanced frequency of a PTPRC (CD45) exon A mutation (77C-->G) in systemic sclerosis. | A point mutation in exon A (C to G transversion at position 77) of human PTPRC (CD45) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that PTPRC could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant PTPRC with other susceptibility genes may uncover mechanisms common in various autoimmune disorders. | Enhanced frequency of a /"PTPRC"/ (/"CD45"/) exon A mutation (77C-->G) in /"systemic sclerosis"/. | A point mutation in exon A (C to G transversion at position 77) of human /"PTPRC"/ (/"CD45"/) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely /"systemic sclerosis"/ (/"SSc"/) and systemic lupus erythematosus (SLE). The mutation was found with significantly enhanced frequency in patients suffering from /"SSc"/ suggesting that /"PTPRC"/ could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant /"PTPRC"/ with other susceptibility genes may uncover mechanisms common in various autoimmune disorders. | [
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} | Yes |
12618866 | Enhanced frequency of a PTPRC (CD45) exon A mutation (77C-->G) in systemic sclerosis. | A point mutation in exon A (C to G transversion at position 77) of human PTPRC (CD45) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that PTPRC could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant PTPRC with other susceptibility genes may uncover mechanisms common in various autoimmune disorders. | Enhanced frequency of a /"PTPRC"/ (/"CD45"/) exon A mutation (77C-->G) in systemic sclerosis. | A point mutation in exon A (C to G transversion at position 77) of human /"PTPRC"/ (/"CD45"/) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely systemic sclerosis (SSc) and /"systemic lupus erythematosus"/ (/"SLE"/). The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that /"PTPRC"/ could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant /"PTPRC"/ with other susceptibility genes may uncover mechanisms common in various autoimmune disorders. | [
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12627470 | Variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha (ERalpha) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective puerperal psychosis. | Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the puerperal period. The estrogen receptor alpha (ERalpha) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or puerperal psychosis. We have examined the frequency of these four ERalpha variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) puerperal psychosis, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the ERalpha variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co-segregation of ERalpha variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERalpha gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis. | Variation in the coding sequence and flanking splice junctions of the /"estrogen receptor alpha"/ (/"ERalpha"/) gene does not play an important role in genetic susceptibility to /"bipolar disorder"/ or bipolar affective puerperal psychosis. | Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to /"bipolar disorder"/ and the affective symptoms suffered by many women during the puerperal period. The /"estrogen receptor alpha"/ (/"ERalpha"/) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with /"bipolar disorder"/ or puerperal psychosis. We have examined the frequency of these four /"ERalpha"/ variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of /"parous bipolar females"/ with (N = 112) and without (N = 50) puerperal psychosis, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the /"ERalpha"/ variations in either the aetiology of /"bipolar disorder"/ or puerperal triggering of /"bipolar episodes"/. Nor did we find co-segregation of /"ERalpha"/ variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the /"ERalpha"/ gene does not play an important pathogenic role in the majority of cases of /"Bipolar Disorder"/ or Bipolar Affective Puerperal Psychosis. | [
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} | Yes |
12627470 | Variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha (ERalpha) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective puerperal psychosis. | Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the puerperal period. The estrogen receptor alpha (ERalpha) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or puerperal psychosis. We have examined the frequency of these four ERalpha variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) puerperal psychosis, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the ERalpha variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co-segregation of ERalpha variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERalpha gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis. | Variation in the coding sequence and flanking splice junctions of the /"estrogen receptor alpha"/ (/"ERalpha"/) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective /"puerperal psychosis"/. | Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the puerperal period. The /"estrogen receptor alpha"/ (/"ERalpha"/) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or /"puerperal psychosis"/. We have examined the frequency of these four /"ERalpha"/ variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) /"puerperal psychosis"/, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the /"ERalpha"/ variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co-segregation of /"ERalpha"/ variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the /"ERalpha"/ gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis. | [
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12631109 | Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. | BACKGROUND: Alport syndrome (AS) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the COL4A3 -/- mouse, an animal model for human AS, we evaluated therapy with ramipril in mice. METHODS: One hundred and twenty-two Alport-mice were treated with 10 mg/kg/day ramipril added to drinking water. Proteinuria, serum-urea and lifespan were monitored. Renal matrix was characterized by immunohistochemistry, light- and electron microscopy, and Western blot. RESULTS: Untreated COL4A3 -/- mice died from renal failure after 71 +/- 6 days. Early therapy starting at four weeks of age and continuing to death delayed onset and reduced the extent of proteinuria. Uremia was postponed by three weeks in treated animals. Lifespan increased by more than 100% to 150 +/- 21 days (P < 0.01). In parallel, decreased deposition of extracellular matrix and lessened interstitial fibrosis as well as reduced amounts of renal transforming growth factor-beta1 (TGF-beta1) could be demonstrated. Late therapy starting at seven weeks decreased proteinuria, however, lifespan did not increase significantly. CONCLUSIONS: The results indicate an antiproteinuric and antifibrotic nephroprotective effect of ramipril in COL4A3 -/- mice is mediated by down-regulation of TGF-beta1. This effect in mice is enhanced by initiation of therapy during pre-symptomatic disease. The data in COL4A3 -/- mice as an animal-model for Alport syndrome suggest that ramipril might as well delay renal failure in humans with AS. Early diagnosis and preemptive treatment also may be crucial in humans. | Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in /"COL4A3"/-knockout mice with /"Alport syndrome"/. | BACKGROUND: /"Alport syndrome"/ (/"AS"/) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the /"COL4A3"/ -/- mouse, an animal model for human /"AS"/, we evaluated therapy with ramipril in mice. METHODS: One hundred and twenty-two Alport-mice were treated with 10 mg/kg/day ramipril added to drinking water. Proteinuria, serum-urea and lifespan were monitored. Renal matrix was characterized by immunohistochemistry, light- and electron microscopy, and Western blot. RESULTS: Untreated /"COL4A3"/ -/- mice died from renal failure after 71 +/- 6 days. Early therapy starting at four weeks of age and continuing to death delayed onset and reduced the extent of proteinuria. Uremia was postponed by three weeks in treated animals. Lifespan increased by more than 100% to 150 +/- 21 days (P < 0.01). In parallel, decreased deposition of extracellular matrix and lessened interstitial fibrosis as well as reduced amounts of renal transforming growth factor-beta1 (TGF-beta1) could be demonstrated. Late therapy starting at seven weeks decreased proteinuria, however, lifespan did not increase significantly. CONCLUSIONS: The results indicate an antiproteinuric and antifibrotic nephroprotective effect of ramipril in /"COL4A3"/ -/- mice is mediated by down-regulation of TGF-beta1. This effect in mice is enhanced by initiation of therapy during pre-symptomatic disease. The data in /"COL4A3"/ -/- mice as an animal-model for /"Alport syndrome"/ suggest that ramipril might as well delay renal failure in humans with /"AS"/. Early diagnosis and preemptive treatment also may be crucial in humans. | [
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12631109 | Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. | BACKGROUND: Alport syndrome (AS) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the COL4A3 -/- mouse, an animal model for human AS, we evaluated therapy with ramipril in mice. METHODS: One hundred and twenty-two Alport-mice were treated with 10 mg/kg/day ramipril added to drinking water. Proteinuria, serum-urea and lifespan were monitored. Renal matrix was characterized by immunohistochemistry, light- and electron microscopy, and Western blot. RESULTS: Untreated COL4A3 -/- mice died from renal failure after 71 +/- 6 days. Early therapy starting at four weeks of age and continuing to death delayed onset and reduced the extent of proteinuria. Uremia was postponed by three weeks in treated animals. Lifespan increased by more than 100% to 150 +/- 21 days (P < 0.01). In parallel, decreased deposition of extracellular matrix and lessened interstitial fibrosis as well as reduced amounts of renal transforming growth factor-beta1 (TGF-beta1) could be demonstrated. Late therapy starting at seven weeks decreased proteinuria, however, lifespan did not increase significantly. CONCLUSIONS: The results indicate an antiproteinuric and antifibrotic nephroprotective effect of ramipril in COL4A3 -/- mice is mediated by down-regulation of TGF-beta1. This effect in mice is enhanced by initiation of therapy during pre-symptomatic disease. The data in COL4A3 -/- mice as an animal-model for Alport syndrome suggest that ramipril might as well delay renal failure in humans with AS. Early diagnosis and preemptive treatment also may be crucial in humans. | Preemptive ramipril therapy delays renal failure and /"reduces renal fibrosis"/ in /"COL4A3"/-knockout mice with Alport syndrome. | BACKGROUND: Alport syndrome (AS) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the /"COL4A3"/ -/- mouse, an animal model for human AS, we evaluated therapy with ramipril in mice. METHODS: One hundred and twenty-two Alport-mice were treated with 10 mg/kg/day ramipril added to drinking water. Proteinuria, serum-urea and lifespan were monitored. Renal matrix was characterized by immunohistochemistry, light- and electron microscopy, and Western blot. RESULTS: Untreated /"COL4A3"/ -/- mice died from renal failure after 71 +/- 6 days. Early therapy starting at four weeks of age and continuing to death delayed onset and reduced the extent of proteinuria. Uremia was postponed by three weeks in treated animals. Lifespan increased by more than 100% to 150 +/- 21 days (P < 0.01). In parallel, decreased deposition of extracellular matrix and lessened interstitial fibrosis as well as reduced amounts of renal transforming growth factor-beta1 (TGF-beta1) could be demonstrated. Late therapy starting at seven weeks decreased proteinuria, however, lifespan did not increase significantly. CONCLUSIONS: The results indicate an antiproteinuric and antifibrotic nephroprotective effect of ramipril in /"COL4A3"/ -/- mice is mediated by down-regulation of TGF-beta1. This effect in mice is enhanced by initiation of therapy during pre-symptomatic disease. The data in /"COL4A3"/ -/- mice as an animal-model for Alport syndrome suggest that ramipril might as well delay renal failure in humans with AS. Early diagnosis and preemptive treatment also may be crucial in humans. | [
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12656452 | Apolipoprotein epsilon4 allele frequency in young Africans of Ugandan descent versus African Americans. | Through its role in lipid metabolism, Apolipoprotein epsilon4 (ApoE4) may affect "brain repair" in stroke, brain hemorrhage, Alzheimer's disease, and other brain injury syndromes for which African Americans may have greater morbidity and mortality. Cross-cultural evaluations of these and other genetic factors may provide insight on possible ethnic differences in risk of morbidity to acute central nervous system (CNS) injury and chronic neurodegenerative processes. As an initial step toward expanding knowledge of ApoE allele frequencies for persons of African descent, we compared ApoE genotype of a group of 70 young Ugandans to 59 (subset of a larger group of 342 African Americans of all ages) age-matched African Americans and to published frequencies for Caucasians and Asians. We found that the ApoE4 and epsilon2 alleles are more frequent in Ugandans (U) than Caucasians (C) or Asians (A) with corresponding alleles showing significant elevations of epsilon2 (U 15.71%, C 8.40%, A 4.20%) and 14 (U 25%, C 13.70%, A 8.90%) (p < .001). Comparing the differences between Ugandans and age-appropriate African Americans (AA) was not statically significant, but this outcome may be due to small sample size. These results provide the only published ApoE frequencies for Ugandans and the complete set of data provides the largest published community group of ApoE frequencies for African Americans. | /"Apolipoprotein epsilon4"/ allele frequency in young Africans of Ugandan descent versus African Americans. | Through its role in lipid metabolism, /"Apolipoprotein epsilon4"/ (/"ApoE4"/) may affect "brain repair" in stroke, brain hemorrhage, Alzheimer's disease, and other brain injury syndromes for which African Americans may have greater morbidity and mortality. Cross-cultural evaluations of these and other genetic factors may provide insight on possible ethnic differences in risk of morbidity to acute central nervous system (CNS) /"injury and chronic neurodegenerative processes"/. As an initial step toward expanding knowledge of /"ApoE"/ allele frequencies for persons of African descent, we compared /"ApoE"/ genotype of a group of 70 young Ugandans to 59 (subset of a larger group of 342 African Americans of all ages) age-matched African Americans and to published frequencies for Caucasians and Asians. We found that the /"ApoE4"/ and epsilon2 alleles are more frequent in Ugandans (U) than Caucasians (C) or Asians (A) with corresponding alleles showing significant elevations of epsilon2 (U 15.71%, C 8.40%, A 4.20%) and 14 (U 25%, C 13.70%, A 8.90%) (p < .001). Comparing the differences between Ugandans and age-appropriate African Americans (AA) was not statically significant, but this outcome may be due to small sample size. These results provide the only published /"ApoE"/ frequencies for Ugandans and the complete set of data provides the largest published community group of /"ApoE"/ frequencies for African Americans. | [
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12656452 | Apolipoprotein epsilon4 allele frequency in young Africans of Ugandan descent versus African Americans. | Through its role in lipid metabolism, Apolipoprotein epsilon4 (ApoE4) may affect "brain repair" in stroke, brain hemorrhage, Alzheimer's disease, and other brain injury syndromes for which African Americans may have greater morbidity and mortality. Cross-cultural evaluations of these and other genetic factors may provide insight on possible ethnic differences in risk of morbidity to acute central nervous system (CNS) injury and chronic neurodegenerative processes. As an initial step toward expanding knowledge of ApoE allele frequencies for persons of African descent, we compared ApoE genotype of a group of 70 young Ugandans to 59 (subset of a larger group of 342 African Americans of all ages) age-matched African Americans and to published frequencies for Caucasians and Asians. We found that the ApoE4 and epsilon2 alleles are more frequent in Ugandans (U) than Caucasians (C) or Asians (A) with corresponding alleles showing significant elevations of epsilon2 (U 15.71%, C 8.40%, A 4.20%) and 14 (U 25%, C 13.70%, A 8.90%) (p < .001). Comparing the differences between Ugandans and age-appropriate African Americans (AA) was not statically significant, but this outcome may be due to small sample size. These results provide the only published ApoE frequencies for Ugandans and the complete set of data provides the largest published community group of ApoE frequencies for African Americans. | /"Apolipoprotein epsilon4"/ allele frequency in young Africans of Ugandan descent versus African Americans. | Through its role in lipid metabolism, /"Apolipoprotein epsilon4"/ (/"ApoE4"/) may affect "brain repair" in stroke, brain hemorrhage, Alzheimer's disease, and other /"brain injury syndromes"/ for which African Americans may have greater morbidity and mortality. Cross-cultural evaluations of these and other genetic factors may provide insight on possible ethnic differences in risk of morbidity to acute central nervous system (CNS) injury and chronic neurodegenerative processes. As an initial step toward expanding knowledge of /"ApoE"/ allele frequencies for persons of African descent, we compared /"ApoE"/ genotype of a group of 70 young Ugandans to 59 (subset of a larger group of 342 African Americans of all ages) age-matched African Americans and to published frequencies for Caucasians and Asians. We found that the /"ApoE4"/ and epsilon2 alleles are more frequent in Ugandans (U) than Caucasians (C) or Asians (A) with corresponding alleles showing significant elevations of epsilon2 (U 15.71%, C 8.40%, A 4.20%) and 14 (U 25%, C 13.70%, A 8.90%) (p < .001). Comparing the differences between Ugandans and age-appropriate African Americans (AA) was not statically significant, but this outcome may be due to small sample size. These results provide the only published /"ApoE"/ frequencies for Ugandans and the complete set of data provides the largest published community group of /"ApoE"/ frequencies for African Americans. | [
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12669197 | T130I mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. | AIMS/HYPOTHESIS: Mutations in hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1). The T130I mutation is a rare missense mutation, which affects a conserved amino acid in a DNA binding domain. This mutation can be found in the general population, so this variant alone does not cause MODY. However, its significance in the development of late-onset Type 2 diabetes is not known. METHODS: We screened 423 unrelated Japanese patients with late-onset Type 2 diabetes and 354 unrelated non-diabetic control subjects for the T130I mutation in the HNF-4alpha gene. The transactivation ability of T130I-HNF-4alpha was assessed using reporter gene assay. RESULTS: The frequency of the T130I mutation was higher in Type 2 diabetic patients ( p=0.015, odds ratio 4.3, 95%CI 1.24-14.98) than control subjects. The serum HDL-cholesterol concentration was lower in Type 2 diabetic patients with the T130I mutation compared with those without this mutation ( p=0.006). Reporter gene analysis showed that T130I-HNF-4alpha transcriptional activity was not impaired compared with wild-type HNF-4alpha in Hela and MIN6 cells, but it was reduced in HepG2 and primary cultured mouse hepatocytes (27-78% of wild type, p<0.05). CONCLUSION/INTERPRETATION: Our findings suggest that T130I-HNF-4alpha is a loss-of-function mutation in hepatocytes and that this mutation is associated with late-onset Type 2 diabetes in Japanese subjects. The T130I mutation in the HNF-4alpha gene might be involved in the development of Type 2 diabetes in the Japanese population. | T130I mutation in /"HNF-4alpha"/ gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. | AIMS/HYPOTHESIS: Mutations in /"hepatocyte nuclear factor (HNF)-4alpha"/ gene cause a form of maturity-onset diabetes of the young (/"MODY1"/). The T130I mutation is a rare missense mutation, which affects a conserved amino acid in a DNA binding domain. This mutation can be found in the general population, so this variant alone does not cause /"MODY"/. However, its significance in the development of late-onset Type 2 diabetes is not known. METHODS: We screened 423 unrelated Japanese patients with late-onset Type 2 diabetes and 354 unrelated non-diabetic control subjects for the T130I mutation in the /"HNF-4alpha"/ gene. The transactivation ability of T130I-/"HNF-4alpha"/ was assessed using reporter gene assay. RESULTS: The frequency of the T130I mutation was higher in Type 2 diabetic patients ( p=0.015, odds ratio 4.3, 95%CI 1.24-14.98) than control subjects. The serum HDL-cholesterol concentration was lower in Type 2 diabetic patients with the T130I mutation compared with those without this mutation ( p=0.006). Reporter gene analysis showed that T130I-/"HNF-4alpha"/ transcriptional activity was not impaired compared with wild-type /"HNF-4alpha"/ in Hela and MIN6 cells, but it was reduced in HepG2 and primary cultured mouse hepatocytes (27-78% of wild type, p<0.05). CONCLUSION/INTERPRETATION: Our findings suggest that T130I-/"HNF-4alpha"/ is a loss-of-function mutation in hepatocytes and that this mutation is associated with late-onset Type 2 diabetes in Japanese subjects. The T130I mutation in the /"HNF-4alpha"/ gene might be involved in the development of Type 2 diabetes in the Japanese population. | [
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12669197 | T130I mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. | AIMS/HYPOTHESIS: Mutations in hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1). The T130I mutation is a rare missense mutation, which affects a conserved amino acid in a DNA binding domain. This mutation can be found in the general population, so this variant alone does not cause MODY. However, its significance in the development of late-onset Type 2 diabetes is not known. METHODS: We screened 423 unrelated Japanese patients with late-onset Type 2 diabetes and 354 unrelated non-diabetic control subjects for the T130I mutation in the HNF-4alpha gene. The transactivation ability of T130I-HNF-4alpha was assessed using reporter gene assay. RESULTS: The frequency of the T130I mutation was higher in Type 2 diabetic patients ( p=0.015, odds ratio 4.3, 95%CI 1.24-14.98) than control subjects. The serum HDL-cholesterol concentration was lower in Type 2 diabetic patients with the T130I mutation compared with those without this mutation ( p=0.006). Reporter gene analysis showed that T130I-HNF-4alpha transcriptional activity was not impaired compared with wild-type HNF-4alpha in Hela and MIN6 cells, but it was reduced in HepG2 and primary cultured mouse hepatocytes (27-78% of wild type, p<0.05). CONCLUSION/INTERPRETATION: Our findings suggest that T130I-HNF-4alpha is a loss-of-function mutation in hepatocytes and that this mutation is associated with late-onset Type 2 diabetes in Japanese subjects. The T130I mutation in the HNF-4alpha gene might be involved in the development of Type 2 diabetes in the Japanese population. | T130I mutation in /"HNF-4alpha"/ gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. | AIMS/HYPOTHESIS: Mutations in /"hepatocyte nuclear factor (HNF)-4alpha"/ gene cause a form of maturity-onset diabetes of the young (/"MODY1"/). The T130I mutation is a rare missense mutation, which affects a conserved amino acid in a DNA binding domain. This mutation can be found in the general population, so this variant alone does not cause MODY. However, its significance in the development of late-onset /"Type"/ 2 diabetes is not known. METHODS: We screened 423 unrelated Japanese patients with late-onset /"Type"/ 2 diabetes and 354 unrelated non-diabetic control subjects for the T130I mutation in the /"HNF-4alpha"/ gene. The transactivation ability of T130I-/"HNF-4alpha"/ was assessed using reporter gene assay. RESULTS: The frequency of the T130I mutation was higher in /"Type"/ 2 diabetic patients ( p=0.015, odds ratio 4.3, 95%CI 1.24-14.98) than control subjects. The serum HDL-cholesterol concentration was lower in /"Type"/ 2 diabetic patients with the T130I mutation compared with those without this mutation ( p=0.006). Reporter gene analysis showed that T130I-/"HNF-4alpha"/ transcriptional activity was not impaired compared with wild-type /"HNF-4alpha"/ in Hela and MIN6 cells, but it was reduced in HepG2 and primary cultured mouse hepatocytes (27-78% of wild type, p<0.05). CONCLUSION/INTERPRETATION: Our findings suggest that T130I-/"HNF-4alpha"/ is a loss-of-function mutation in hepatocytes and that this mutation is associated with late-onset /"Type"/ 2 diabetes in Japanese subjects. The T130I mutation in the /"HNF-4alpha"/ gene might be involved in the development of /"Type"/ 2 diabetes in the Japanese population. | [
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12679452 | Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. | Estrogen exposure has repeatedly been shown to associate with the risk of developing breast cancer. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (LHR), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype. A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 breast cancers. The LHR18insLQ allele does not seem to influence breast cancer risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type LHR allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger tumor size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for LHR [hazard ratio = 2.4; 95% CI (1.3-4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer. | Luteinizing hormone signaling and /"breast cancer"/: polymorphisms and age of onset. | Estrogen exposure has repeatedly been shown to associate with the risk of developing /"breast cancer"/. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (/"LHR"/), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of /"breast cancer"/ or its clinical phenotype. A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 /"breast cancers"/. The LHR18insLQ allele does not seem to influence /"breast cancer"/ risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type /"LHR"/ allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger tumor size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for /"LHR"/ [hazard ratio = 2.4; 95% CI (1.3-4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of /"breast cancer"/. | [
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} | Yes |
12679452 | Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. | Estrogen exposure has repeatedly been shown to associate with the risk of developing breast cancer. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (LHR), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype. A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 breast cancers. The LHR18insLQ allele does not seem to influence breast cancer risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type LHR allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger tumor size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for LHR [hazard ratio = 2.4; 95% CI (1.3-4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer. | Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. | Estrogen exposure has repeatedly been shown to associate with the risk of developing breast cancer. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (/"LHR"/), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype. A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 breast cancers. The LHR18insLQ allele does not seem to influence breast cancer risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type /"LHR"/ allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger /"tumor"/ size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for /"LHR"/ [hazard ratio = 2.4; 95% CI (1.3-4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer. | [
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12684755 | Interaction of CA repeat polymorphism of the endothelial nitric oxide synthase and hyperhomocysteinemia in acute coronary syndromes: evidence of gender-specific differences. | We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring endothelial dysfunction. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and acute coronary syndromes. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of acute coronary syndromes for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with acute coronary syndromes. Although the CA repeat copy numbers were not associated with acute coronary syndromes in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing acute coronary syndromes increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in acute coronary syndromes. | Interaction of CA repeat polymorphism of the /"endothelial nitric oxide synthase"/ and hyperhomocysteinemia in /"acute coronary syndromes"/: evidence of gender-specific differences. | We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring endothelial dysfunction. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and /"acute coronary syndromes"/. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of /"acute coronary syndromes"/ for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with /"acute coronary syndromes"/. Although the CA repeat copy numbers were not associated with /"acute coronary syndromes"/ in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing /"acute coronary syndromes"/ increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in /"acute coronary syndromes"/. | [
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"text_name": "acute coronary syndromes"
} | Yes |
12684755 | Interaction of CA repeat polymorphism of the endothelial nitric oxide synthase and hyperhomocysteinemia in acute coronary syndromes: evidence of gender-specific differences. | We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring endothelial dysfunction. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and acute coronary syndromes. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of acute coronary syndromes for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with acute coronary syndromes. Although the CA repeat copy numbers were not associated with acute coronary syndromes in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing acute coronary syndromes increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in acute coronary syndromes. | Interaction of CA repeat polymorphism of the /"endothelial nitric oxide synthase"/ and hyperhomocysteinemia in acute coronary syndromes: evidence of gender-specific differences. | We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring /"endothelial dysfunction"/. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and acute coronary syndromes. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of acute coronary syndromes for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with acute coronary syndromes. Although the CA repeat copy numbers were not associated with acute coronary syndromes in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing acute coronary syndromes increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in acute coronary syndromes. | [
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12694583 | The association of HLA -A, -B, and -DRB1 genotypes with Graves' disease in Taiwanese people. | Graves' disease has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with Graves' disease, the HLA-A, -B, and -DRB1 alleles in a total of 236 Taiwanese adults with Graves' disease and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -DRB1*0901 among patients with Graves' disease was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to Graves' disease remained statistically significant and the haplotype HLA-A*3303 -B*5801 -DRB1*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although HLA-DRB1*1405 showed an increased relative risk in patients with GO (Graves' opthalmopathy) (OR 4.61) when compared with patients without GO, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with Graves' disease have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with Graves' disease has not been documented in any other ethnic group. | The association of HLA -A, -B, and -/"DRB1"/ genotypes with /"Graves' disease"/ in Taiwanese people. | /"Graves' disease"/ has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with /"Graves' disease"/, the /"HLA-A, -B, and -DRB1"/ alleles in a total of 236 Taiwanese adults with /"Graves' disease"/ and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -/"DRB1"/*0901 among patients with /"Graves' disease"/ was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to /"Graves' disease"/ remained statistically significant and the haplotype HLA-A*3303 -B*5801 -/"DRB1"/*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although /"HLA-DRB1"/*1405 showed an increased relative risk in patients with /"GO"/ (/"Graves' opthalmopathy"/) (OR 4.61) when compared with patients without /"GO"/, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with /"Graves' disease"/ have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with /"Graves' disease"/ has not been documented in any other ethnic group. | [
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} | Yes |
12694583 | The association of HLA -A, -B, and -DRB1 genotypes with Graves' disease in Taiwanese people. | Graves' disease has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with Graves' disease, the HLA-A, -B, and -DRB1 alleles in a total of 236 Taiwanese adults with Graves' disease and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -DRB1*0901 among patients with Graves' disease was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to Graves' disease remained statistically significant and the haplotype HLA-A*3303 -B*5801 -DRB1*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although HLA-DRB1*1405 showed an increased relative risk in patients with GO (Graves' opthalmopathy) (OR 4.61) when compared with patients without GO, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with Graves' disease have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with Graves' disease has not been documented in any other ethnic group. | The association of HLA -A, -B, and -DRB1 genotypes with /"Graves' disease"/ in Taiwanese people. | /"Graves' disease"/ has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with /"Graves' disease"/, the /"HLA-A, -B, and -DRB1"/ alleles in a total of 236 Taiwanese adults with /"Graves' disease"/ and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -DRB1*0901 among patients with /"Graves' disease"/ was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to /"Graves' disease"/ remained statistically significant and the haplotype HLA-A*3303 -B*5801 -DRB1*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although HLA-DRB1*1405 showed an increased relative risk in patients with /"GO"/ (/"Graves' opthalmopathy"/) (OR 4.61) when compared with patients without /"GO"/, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with /"Graves' disease"/ have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with /"Graves' disease"/ has not been documented in any other ethnic group. | [
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} | Yes |
12694583 | The association of HLA -A, -B, and -DRB1 genotypes with Graves' disease in Taiwanese people. | Graves' disease has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with Graves' disease, the HLA-A, -B, and -DRB1 alleles in a total of 236 Taiwanese adults with Graves' disease and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -DRB1*0901 among patients with Graves' disease was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to Graves' disease remained statistically significant and the haplotype HLA-A*3303 -B*5801 -DRB1*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although HLA-DRB1*1405 showed an increased relative risk in patients with GO (Graves' opthalmopathy) (OR 4.61) when compared with patients without GO, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with Graves' disease have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with Graves' disease has not been documented in any other ethnic group. | The association of HLA -A, -B, and -DRB1 genotypes with /"Graves' disease"/ in Taiwanese people. | /"Graves' disease"/ has been associated with different human leukocyte antigen (HLA) genes in different races. To evaluate the association of HLA type in Taiwanese with /"Graves' disease"/, the /"HLA-A, -B, and -DRB1"/ alleles in a total of 236 Taiwanese adults with /"Graves' disease"/ and 533 racially matched normal control subjects were examined using the PCR-SSOP (sequence specific oligonucleotide probe) technique. The prevalence of HLA-A*0207, -B*2704, -B*4601, and -DRB1*0901 among patients with /"Graves' disease"/ was found to be increased, with odds ratios (OR) of 2.21, 3.82, 1.76 and 1.62, respectively. However, after correction for multiple comparisons, the relative risk of HLA-A*0207 susceptibility to /"Graves' disease"/ remained statistically significant and the haplotype HLA-A*3303 -B*5801 -DRB1*0301 had a significantly protective effect. None of the other 2- or 3-locus haplotypes showed any significantly increased risk. Although HLA-DRB1*1405 showed an increased relative risk in patients with /"GO"/ (/"Graves' opthalmopathy"/) (OR 4.61) when compared with patients without /"GO"/, the relative risk after adjusting for the number of comparisons was not significant. Taiwanese patients with /"Graves' disease"/ have HLA-associated susceptibility genes which are similar to those found in Chinese patients in Hong Kong and Singapore. However, the finding in this study of a higher frequency of HLA-A*0207 in Taiwanese with /"Graves' disease"/ has not been documented in any other ethnic group. | [
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12699434 | Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing's disease. | Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received corticotrophin-releasing hormone (CRH). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that CRH administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy. | Pituitary apoplexy induced by /"corticotrophin-releasing hormone"/ in a patient with Cushing's disease. | Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received /"corticotrophin-releasing hormone"/ (/"CRH"/). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of /"pituitary apoplexy"/ was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that /"CRH"/ administration can induce /"pituitary apoplexy"/ in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with /"pituitary apoplexy"/. | [
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12699434 | Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing's disease. | Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received corticotrophin-releasing hormone (CRH). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that CRH administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy. | Pituitary apoplexy induced by /"corticotrophin-releasing hormone"/ in a patient with Cushing's disease. | Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received /"corticotrophin-releasing hormone"/ (/"CRH"/). Two days later she developed severe headache, accompanied by /"nausea"/ and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that /"CRH"/ administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy. | [
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12714823 | Prevalence of hemochromatosis gene (HFE) mutations in Greece. | The frequencies of the hereditary hemochromatosis gene (HFE) mutations C282Y and H63D vary between different populations. There are a limited number of reports regarding the frequency of these mutations in populations of southeastern Europe. Two hundred and sixty-four adult individuals of Greek origin were examined for the C282Y and H63D mutations to determine the allele and genotype frequencies. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by the polymerase chain reaction. Restriction enzyme analysis was performed using RSAI for C282Y and MBOI for H63D. None of the 264 individuals carried the mutation C282Y. Forty-three individuals (16.2%) were heterozygous carriers of the H63D allele and 2 were homozygous for this mutation (0.75%). The overall H63D allele prevalence is thus estimated at 8.9%. HFE mutation frequencies were low in the population studied and this may explain, in part, the relative rarity of clinical cases of hereditary hemochromatosis in Greece. | Prevalence of /"hemochromatosis"/is"/ gene (/"HFE"/) mutations in Greece. | The frequencies of the /"hereditary hemochromatosis"/is"/ gene (/"HFE"/) mutations C282Y and H63D vary between different populations. There are a limited number of reports regarding the frequency of these mutations in populations of southeastern Europe. Two hundred and sixty-four adult individuals of Greek origin were examined for the C282Y and H63D mutations to determine the allele and genotype frequencies. The /"HFE"/ gene region of DNA samples extracted from peripheral leukocytes was amplified by the polymerase chain reaction. Restriction enzyme analysis was performed using RSAI for C282Y and MBOI for H63D. None of the 264 individuals carried the mutation C282Y. Forty-three individuals (16.2%) were heterozygous carriers of the H63D allele and 2 were homozygous for this mutation (0.75%). The overall H63D allele prevalence is thus estimated at 8.9%. /"HFE"/ mutation frequencies were low in the population studied and this may explain, in part, the relative rarity of clinical cases of /"hereditary hemochromatosis"/is"/ in Greece. | [
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12716762 | The peroxisome proliferator-activated receptor-gamma2 gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study. | The peroxisome proliferator-activated receptor (PPAR)-gamma2 gene polymorphism Pro12Ala has been associated with increased insulin sensitivity in some but not all studies. Little is known about its effect on the tracking of insulin resistance status over time. These aspects were examined in a community-based sample of 686 white young adults, aged 20-38 years, and 426 white children, aged 4-17 years, and a subsample of a cohort (n = 362) who participated both as children and adults, with an average follow-up period of 13.4 years. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin and glucose. The frequency of the variant Ala12 allele was 0.104 in whites vs. 0.017 in blacks. After adjusting for sex, age, and BMI, adult subjects with the genotype Pro/Pro, Pro/Ala, and Ala/Ala, respectively, showed significant decreasing trends in fasting insulin (11.7, 10.3, and 8.8 micro U/ml; P = 0.002) and HOMA-IR (2.4, 2.1, and 1.7; P = 0.006). Similar but nonsignificant trends were noted in childhood. A significant genotype-BMI interaction effect on insulin (P = 0.020), glucose (P = 0.007), and HOMA-IR (P = 0.001) was found in adulthood, with carriers versus noncarriers showing attenuated association with BMI. The genotype-BMI interaction effect on these variables tended to be similar in childhood. With respect to tracking over time, of individuals in the top age- and sex-specific quartile of HOMA-IR in childhood, 48.7% (38/78) of noncarriers vs. 16.7% (2/12) of the carriers (P = 0.035) remained in the same quartile in adulthood. A similar trend was observed for insulin (2/13 vs. 35/77, P = 0.037). In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene beneficially influences insulin resistance and its tracking from childhood to adulthood. Further, the Ala12 allele attenuates the adverse association between adiposity and insulin resistance measures. | The /"peroxisome proliferator-activated receptor-gamma2"/ gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study. | The /"peroxisome proliferator-activated receptor (PPAR)-gamma2"/ gene polymorphism Pro12Ala has been associated with /"increased insulin sensitivity"/ in some but not all studies. Little is known about its effect on the tracking of insulin resistance status over time. These aspects were examined in a community-based sample of 686 white young adults, aged 20-38 years, and 426 white children, aged 4-17 years, and a subsample of a cohort (n = 362) who participated both as children and adults, with an average follow-up period of 13.4 years. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin and glucose. The frequency of the variant Ala12 allele was 0.104 in whites vs. 0.017 in blacks. After adjusting for sex, age, and BMI, adult subjects with the genotype Pro/Pro, Pro/Ala, and Ala/Ala, respectively, showed significant decreasing trends in fasting insulin (11.7, 10.3, and 8.8 micro U/ml; P = 0.002) and HOMA-IR (2.4, 2.1, and 1.7; P = 0.006). Similar but nonsignificant trends were noted in childhood. A significant genotype-BMI interaction effect on insulin (P = 0.020), glucose (P = 0.007), and HOMA-IR (P = 0.001) was found in adulthood, with carriers versus noncarriers showing attenuated association with BMI. The genotype-BMI interaction effect on these variables tended to be similar in childhood. With respect to tracking over time, of individuals in the top age- and sex-specific quartile of HOMA-IR in childhood, 48.7% (38/78) of noncarriers vs. 16.7% (2/12) of the carriers (P = 0.035) remained in the same quartile in adulthood. A similar trend was observed for insulin (2/13 vs. 35/77, P = 0.037). In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene beneficially influences insulin resistance and its tracking from childhood to adulthood. Further, the Ala12 allele attenuates the adverse association between adiposity and insulin resistance measures. | [
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12716762 | The peroxisome proliferator-activated receptor-gamma2 gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study. | The peroxisome proliferator-activated receptor (PPAR)-gamma2 gene polymorphism Pro12Ala has been associated with increased insulin sensitivity in some but not all studies. Little is known about its effect on the tracking of insulin resistance status over time. These aspects were examined in a community-based sample of 686 white young adults, aged 20-38 years, and 426 white children, aged 4-17 years, and a subsample of a cohort (n = 362) who participated both as children and adults, with an average follow-up period of 13.4 years. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin and glucose. The frequency of the variant Ala12 allele was 0.104 in whites vs. 0.017 in blacks. After adjusting for sex, age, and BMI, adult subjects with the genotype Pro/Pro, Pro/Ala, and Ala/Ala, respectively, showed significant decreasing trends in fasting insulin (11.7, 10.3, and 8.8 micro U/ml; P = 0.002) and HOMA-IR (2.4, 2.1, and 1.7; P = 0.006). Similar but nonsignificant trends were noted in childhood. A significant genotype-BMI interaction effect on insulin (P = 0.020), glucose (P = 0.007), and HOMA-IR (P = 0.001) was found in adulthood, with carriers versus noncarriers showing attenuated association with BMI. The genotype-BMI interaction effect on these variables tended to be similar in childhood. With respect to tracking over time, of individuals in the top age- and sex-specific quartile of HOMA-IR in childhood, 48.7% (38/78) of noncarriers vs. 16.7% (2/12) of the carriers (P = 0.035) remained in the same quartile in adulthood. A similar trend was observed for insulin (2/13 vs. 35/77, P = 0.037). In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene beneficially influences insulin resistance and its tracking from childhood to adulthood. Further, the Ala12 allele attenuates the adverse association between adiposity and insulin resistance measures. | The /"peroxisome proliferator-activated receptor-gamma2"/ gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study. | The /"peroxisome proliferator-activated receptor (PPAR)-gamma2"/ gene polymorphism Pro12Ala has been associated with increased insulin sensitivity in some but not all studies. Little is known about its effect on the tracking of insulin resistance status over time. These aspects were examined in a community-based sample of 686 white young adults, aged 20-38 years, and 426 white children, aged 4-17 years, and a subsample of a cohort (n = 362) who participated both as children and adults, with an average follow-up period of 13.4 years. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin and glucose. The frequency of the variant Ala12 allele was 0.104 in whites vs. 0.017 in blacks. After adjusting for sex, age, and BMI, adult subjects with the genotype Pro/Pro, Pro/Ala, and Ala/Ala, respectively, showed significant decreasing trends in fasting insulin (11.7, 10.3, and 8.8 micro U/ml; P = 0.002) and HOMA-IR (2.4, 2.1, and 1.7; P = 0.006). Similar but nonsignificant trends were noted in childhood. A significant genotype-BMI interaction effect on insulin (P = 0.020), glucose (P = 0.007), and HOMA-IR (P = 0.001) was found in adulthood, with carriers versus noncarriers showing attenuated association with BMI. The genotype-BMI interaction effect on these variables tended to be similar in childhood. With respect to tracking over time, of individuals in the top age- and sex-specific quartile of HOMA-IR in childhood, 48.7% (38/78) of noncarriers vs. 16.7% (2/12) of the carriers (P = 0.035) remained in the same quartile in adulthood. A similar trend was observed for insulin (2/13 vs. 35/77, P = 0.037). In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene beneficially influences insulin resistance and its tracking from childhood to adulthood. Further, the Ala12 allele attenuates the adverse association between /"adiposity"/ and insulin resistance measures. | [
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12728591 | [Effect of ACE gene polymorphism on left ventricular function in patients with type 2 diabetes]. | The authors evaluated the influence of the ACE gene polymorphism on left ventricular function in patients with diabetes type 2. In a group of 23 patients left ventricular mass, global and regional systolic function of the left ventricle as well as diastolic function was assessed from transmitral flow using two-dimensional echocardiography. In a subgroup of patients with DD (n = 7) and ID genotype (n = 16), no significant differences were found in age (p = 0.19), duration of diabetes (p = 0.46), level of HbA1c (p = 0.10), cholesterol level (p = 0.18), quantitative proteinuria (p = 0.39), systolic and diastolic blood pressure (p = 0.25, p = 0.40). No association was found between insertion-deletion polymorphism of the ACE gene and observed echocardiographic parameters [left ventricular mass index (p = 0.43), EF (p = 0.46), wall motion index (p = 0.25), E wave (p = 0.14), A wave (p = 0.07), deceleration time of the E wave (p = 0.06), E/A (p = 0.07), flow propagation velocity (Vp) (p = 0.14) and E/Vp (p = 0.38)]. The presence of myocardial infarction, ischemic heart disease and hypertension had no association with ACE gene polymorphism (p = 0.53, p = 0.61 and p = 0.64). In conclusion, there is no association between ACE gene polymorphism and systolic and diastolic function of the left ventricle in this group of patients with diabetes type 2. | [Effect of /"ACE"/ gene polymorphism on left ventricular function in patients with type 2 diabetes]. | The authors evaluated the influence of the /"ACE"/ gene polymorphism on left ventricular function in patients with /"diabetes type 2"/. In a group of 23 patients left ventricular mass, global and regional systolic function of the left ventricle as well as diastolic function was assessed from transmitral flow using two-dimensional echocardiography. In a subgroup of patients with DD (n = 7) and ID genotype (n = 16), no significant differences were found in age (p = 0.19), duration of diabetes (p = 0.46), level of HbA1c (p = 0.10), cholesterol level (p = 0.18), quantitative proteinuria (p = 0.39), systolic and diastolic blood pressure (p = 0.25, p = 0.40). No association was found between insertion-deletion polymorphism of the /"ACE"/ gene and observed echocardiographic parameters [left ventricular mass index (p = 0.43), EF (p = 0.46), wall motion index (p = 0.25), E wave (p = 0.14), A wave (p = 0.07), deceleration time of the E wave (p = 0.06), E/A (p = 0.07), flow propagation velocity (Vp) (p = 0.14) and E/Vp (p = 0.38)]. The presence of myocardial infarction, ischemic heart disease and hypertension had no association with /"ACE"/ gene polymorphism (p = 0.53, p = 0.61 and p = 0.64). In conclusion, there is no association between /"ACE"/ gene polymorphism and systolic and diastolic function of the left ventricle in this group of patients with /"diabetes type 2"/. | [
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12728591 | [Effect of ACE gene polymorphism on left ventricular function in patients with type 2 diabetes]. | The authors evaluated the influence of the ACE gene polymorphism on left ventricular function in patients with diabetes type 2. In a group of 23 patients left ventricular mass, global and regional systolic function of the left ventricle as well as diastolic function was assessed from transmitral flow using two-dimensional echocardiography. In a subgroup of patients with DD (n = 7) and ID genotype (n = 16), no significant differences were found in age (p = 0.19), duration of diabetes (p = 0.46), level of HbA1c (p = 0.10), cholesterol level (p = 0.18), quantitative proteinuria (p = 0.39), systolic and diastolic blood pressure (p = 0.25, p = 0.40). No association was found between insertion-deletion polymorphism of the ACE gene and observed echocardiographic parameters [left ventricular mass index (p = 0.43), EF (p = 0.46), wall motion index (p = 0.25), E wave (p = 0.14), A wave (p = 0.07), deceleration time of the E wave (p = 0.06), E/A (p = 0.07), flow propagation velocity (Vp) (p = 0.14) and E/Vp (p = 0.38)]. The presence of myocardial infarction, ischemic heart disease and hypertension had no association with ACE gene polymorphism (p = 0.53, p = 0.61 and p = 0.64). In conclusion, there is no association between ACE gene polymorphism and systolic and diastolic function of the left ventricle in this group of patients with diabetes type 2. | [Effect of /"ACE"/ gene polymorphism on left ventricular function in patients with type 2 diabetes]. | The authors evaluated the influence of the /"ACE"/ gene polymorphism on left ventricular function in patients with diabetes type 2. In a group of 23 patients left ventricular mass, global and regional systolic function of the left ventricle as well as diastolic function was assessed from transmitral flow using two-dimensional echocardiography. In a subgroup of patients with DD (n = 7) and ID genotype (n = 16), no significant differences were found in age (p = 0.19), duration of diabetes (p = 0.46), level of HbA1c (p = 0.10), cholesterol level (p = 0.18), quantitative /"proteinuria"/ (p = 0.39), systolic and diastolic blood pressure (p = 0.25, p = 0.40). No association was found between insertion-deletion polymorphism of the /"ACE"/ gene and observed echocardiographic parameters [left ventricular mass index (p = 0.43), EF (p = 0.46), wall motion index (p = 0.25), E wave (p = 0.14), A wave (p = 0.07), deceleration time of the E wave (p = 0.06), E/A (p = 0.07), flow propagation velocity (Vp) (p = 0.14) and E/Vp (p = 0.38)]. The presence of myocardial infarction, ischemic heart disease and hypertension had no association with /"ACE"/ gene polymorphism (p = 0.53, p = 0.61 and p = 0.64). In conclusion, there is no association between /"ACE"/ gene polymorphism and systolic and diastolic function of the left ventricle in this group of patients with diabetes type 2. | [
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12728975 | Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. | BACKGROUND: This study compared the polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene between type II diabetes with diabetic nephropathy (DN) in end-stage renal disease (ESRD) and those of the normal individuals in Taiwan. METHODS: 129 patients with type II diabetes in ESRD from three dialysis centers were compared to 116 age and blood pressure-matched normal individuals. Polymerase chain reaction (PCR) specific for ACE gene was tested for insertion/deletion polymorphism. M235T and T174M variant polymorphisms of the AGT gene and the AT1R A1166C polymorphism were also tested according to previously described protocols. RESULTS: Between the two groups, frequencies of the alleles and the genotypes in ACE gene polymorphism were comparable. There was no significant difference of the ACE insertion and deletion polymorphism and AT1R gene polymorphism between the two groups. The allele frequencies of AGT point mutation at 235 (M235T) was significantly higher in DM nephropathy but the genotypic frequencies were not. In the AGT point mutation at 174 (T174M), the frequencies of both of alleles and genotypes were significantly higher in the DM nephropathy patients. CONCLUSIONS: In conclusion, there were significantly higher frequencies of alleles and genotypes in AGT point mutation at 174, which had never been reported before. In AGT point mutation at 235, there were significantly higher frequencies of alleles, but not genotypes in diabetic nephropathy. Our study suggested that the AGT gene plays an important role in diabetic nephropathy. | Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in /"type II diabetes"/ with end-stage renal disease in Taiwan. | BACKGROUND: This study compared the polymorphisms of /"angiotensin-converting enzyme"/ (/"ACE"/), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene between /"type II diabetes"/ with diabetic nephropathy (DN) in end-stage renal disease (ESRD) and those of the normal individuals in Taiwan. METHODS: 129 patients with /"type II diabetes"/ in ESRD from three dialysis centers were compared to 116 age and blood pressure-matched normal individuals. Polymerase chain reaction (PCR) specific for /"ACE"/ gene was tested for insertion/deletion polymorphism. M235T and T174M variant polymorphisms of the AGT gene and the AT1R A1166C polymorphism were also tested according to previously described protocols. RESULTS: Between the two groups, frequencies of the alleles and the genotypes in /"ACE"/ gene polymorphism were comparable. There was no significant difference of the /"ACE"/ insertion and deletion polymorphism and AT1R gene polymorphism between the two groups. The allele frequencies of AGT point mutation at 235 (M235T) was significantly higher in DM nephropathy but the genotypic frequencies were not. In the AGT point mutation at 174 (T174M), the frequencies of both of alleles and genotypes were significantly higher in the DM nephropathy patients. CONCLUSIONS: In conclusion, there were significantly higher frequencies of alleles and genotypes in AGT point mutation at 174, which had never been reported before. In AGT point mutation at 235, there were significantly higher frequencies of alleles, but not genotypes in diabetic nephropathy. Our study suggested that the AGT gene plays an important role in diabetic nephropathy. | [
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12728975 | Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. | BACKGROUND: This study compared the polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene between type II diabetes with diabetic nephropathy (DN) in end-stage renal disease (ESRD) and those of the normal individuals in Taiwan. METHODS: 129 patients with type II diabetes in ESRD from three dialysis centers were compared to 116 age and blood pressure-matched normal individuals. Polymerase chain reaction (PCR) specific for ACE gene was tested for insertion/deletion polymorphism. M235T and T174M variant polymorphisms of the AGT gene and the AT1R A1166C polymorphism were also tested according to previously described protocols. RESULTS: Between the two groups, frequencies of the alleles and the genotypes in ACE gene polymorphism were comparable. There was no significant difference of the ACE insertion and deletion polymorphism and AT1R gene polymorphism between the two groups. The allele frequencies of AGT point mutation at 235 (M235T) was significantly higher in DM nephropathy but the genotypic frequencies were not. In the AGT point mutation at 174 (T174M), the frequencies of both of alleles and genotypes were significantly higher in the DM nephropathy patients. CONCLUSIONS: In conclusion, there were significantly higher frequencies of alleles and genotypes in AGT point mutation at 174, which had never been reported before. In AGT point mutation at 235, there were significantly higher frequencies of alleles, but not genotypes in diabetic nephropathy. Our study suggested that the AGT gene plays an important role in diabetic nephropathy. | Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. | BACKGROUND: This study compared the polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and /"angiotensin II type 1 receptor"/ (/"AT1R"/) gene between type II diabetes with /"diabetic nephropathy"/ (/"DN"/) in end-stage renal disease (ESRD) and those of the normal individuals in Taiwan. METHODS: 129 patients with type II diabetes in ESRD from three dialysis centers were compared to 116 age and blood pressure-matched normal individuals. Polymerase chain reaction (PCR) specific for ACE gene was tested for insertion/deletion polymorphism. M235T and T174M variant polymorphisms of the AGT gene and the /"AT1R"/ A1166C polymorphism were also tested according to previously described protocols. RESULTS: Between the two groups, frequencies of the alleles and the genotypes in ACE gene polymorphism were comparable. There was no significant difference of the ACE insertion and deletion polymorphism and /"AT1R"/ gene polymorphism between the two groups. The allele frequencies of AGT point mutation at 235 (M235T) was significantly higher in DM nephropathy but the genotypic frequencies were not. In the AGT point mutation at 174 (T174M), the frequencies of both of alleles and genotypes were significantly higher in the DM nephropathy patients. CONCLUSIONS: In conclusion, there were significantly higher frequencies of alleles and genotypes in AGT point mutation at 174, which had never been reported before. In AGT point mutation at 235, there were significantly higher frequencies of alleles, but not genotypes in /"diabetic nephropathy"/. Our study suggested that the AGT gene plays an important role in /"diabetic nephropathy"/. | [
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12746438 | Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. | It has long been recognized that muscarinic acetylcholine receptors (mAChRs) are crucial for the control of cognitive processes, and drugs that activate mAChRs are helpful in ameliorating cognitive deficits of Alzheimer's disease (AD). On the other hand, GABAergic transmission in prefrontal cortex (PFC) plays a key role in "working memory" via controlling the timing of neuronal activity during cognitive operations. To test whether the muscarinic and gamma-aminobutyric acid (GABA) system are interconnected in normal cognition and dementia, we examined the muscarinic regulation of GABAergic transmission in PFC of an animal model of AD. Transgenic mice overexpressing a mutant gene for beta-amyloid precursor protein (APP) show behavioral and histopathological abnormalities resembling AD and, therefore, were used as an AD model. Application of the mAChR agonist carbachol significantly increased the spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude in PFC pyramidal neurons from wild-type animals. In contrast, carbachol failed to increase the sIPSC amplitude in APP transgenic mice, whereas the carbachol-induced increase of the sIPSC frequency was not significantly changed in these mutants. Similar results were obtained in rat PFC slices pretreated with the beta-amyloid peptide (Abeta). Inhibiting protein kinase C (PKC) blocked the carbachol enhancement of sIPSC amplitudes, implicating the PKC dependence of this mAChR effect. In APP transgenic mice, carbachol failed to activate PKC despite the apparently normal expression of mAChRs. These results show that the muscarinic regulation of GABA transmission is impaired in the AD model, probably due to the Abeta-mediated interference of mAChR activation of PKC. | Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of /"Alzheimer's disease"/. | It has long been recognized that muscarinic acetylcholine receptors (mAChRs) are crucial for the control of cognitive processes, and drugs that activate mAChRs are helpful in ameliorating cognitive deficits of /"Alzheimer's disease"/ (/"AD"/). On the other hand, GABAergic transmission in prefrontal cortex (PFC) plays a key role in "working memory" via controlling the timing of neuronal activity during cognitive operations. To test whether the muscarinic and gamma-aminobutyric acid (GABA) system are interconnected in normal cognition and dementia, we examined the muscarinic regulation of GABAergic transmission in PFC of an animal model of /"AD"/. Transgenic mice overexpressing a mutant gene for /"beta-amyloid precursor protein"/ (/"APP"/) show behavioral and histopathological abnormalities resembling /"AD"/ and, therefore, were used as an /"AD"/ model. Application of the mAChR agonist carbachol significantly increased the spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude in PFC pyramidal neurons from wild-type animals. In contrast, carbachol failed to increase the sIPSC amplitude in /"APP"/ transgenic mice, whereas the carbachol-induced increase of the sIPSC frequency was not significantly changed in these mutants. Similar results were obtained in rat PFC slices pretreated with the beta-amyloid peptide (Abeta). Inhibiting protein kinase C (PKC) blocked the carbachol enhancement of sIPSC amplitudes, implicating the PKC dependence of this mAChR effect. In /"APP"/ transgenic mice, carbachol failed to activate PKC despite the apparently normal expression of mAChRs. These results show that the muscarinic regulation of GABA transmission is impaired in the /"AD"/ model, probably due to the Abeta-mediated interference of mAChR activation of PKC. | [
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12746438 | Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. | It has long been recognized that muscarinic acetylcholine receptors (mAChRs) are crucial for the control of cognitive processes, and drugs that activate mAChRs are helpful in ameliorating cognitive deficits of Alzheimer's disease (AD). On the other hand, GABAergic transmission in prefrontal cortex (PFC) plays a key role in "working memory" via controlling the timing of neuronal activity during cognitive operations. To test whether the muscarinic and gamma-aminobutyric acid (GABA) system are interconnected in normal cognition and dementia, we examined the muscarinic regulation of GABAergic transmission in PFC of an animal model of AD. Transgenic mice overexpressing a mutant gene for beta-amyloid precursor protein (APP) show behavioral and histopathological abnormalities resembling AD and, therefore, were used as an AD model. Application of the mAChR agonist carbachol significantly increased the spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude in PFC pyramidal neurons from wild-type animals. In contrast, carbachol failed to increase the sIPSC amplitude in APP transgenic mice, whereas the carbachol-induced increase of the sIPSC frequency was not significantly changed in these mutants. Similar results were obtained in rat PFC slices pretreated with the beta-amyloid peptide (Abeta). Inhibiting protein kinase C (PKC) blocked the carbachol enhancement of sIPSC amplitudes, implicating the PKC dependence of this mAChR effect. In APP transgenic mice, carbachol failed to activate PKC despite the apparently normal expression of mAChRs. These results show that the muscarinic regulation of GABA transmission is impaired in the AD model, probably due to the Abeta-mediated interference of mAChR activation of PKC. | Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. | It has long been recognized that muscarinic acetylcholine receptors (mAChRs) are crucial for the control of cognitive processes, and drugs that activate mAChRs are helpful in ameliorating cognitive deficits of Alzheimer's disease (AD). On the other hand, GABAergic transmission in prefrontal cortex (PFC) plays a key role in "working memory" via controlling the timing of neuronal activity during cognitive operations. To test whether the muscarinic and gamma-aminobutyric acid (GABA) system are interconnected in normal cognition and dementia, we examined the muscarinic regulation of GABAergic transmission in PFC of an animal model of AD. Transgenic mice overexpressing a mutant gene for /"beta-amyloid precursor protein"/ (/"APP"/) show behavioral and histopathological abnormalities resembling AD and, therefore, were used as an AD model. Application of the mAChR agonist carbachol significantly increased the spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude in PFC pyramidal neurons from wild-type animals. In contrast, carbachol failed to increase the sIPSC amplitude in /"APP"/ transgenic mice, whereas the carbachol-induced increase of the sIPSC frequency was not significantly changed in these mutants. Similar results were obtained in rat PFC slices pretreated with the beta-amyloid peptide (Abeta). Inhibiting /"protein kinase C"/ (/"PKC"/) blocked the carbachol enhancement of sIPSC amplitudes, implicating the /"PKC"/ dependence of this mAChR effect. In /"APP"/ transgenic mice, carbachol failed to activate /"PKC"/ despite the apparently normal expression of mAChRs. These results show that the muscarinic regulation of GABA transmission is impaired in the AD model, probably due to the Abeta-mediated interference of mAChR activation of /"PKC"/. | [
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12747597 | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and /"angiotensin-II type 1 receptor"/ gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the /"angiotensin-II type 1 receptor"/ gene polymorphisms (A1166C /"AT1R"/) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C /"AT1R"/ genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C /"AT1R"/ genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior /"myocardial infarction"/ with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and /"AT1R"/ A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | [
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12747597 | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and /"angiotensin-II type 1 receptor"/ gene polymorphisms in patients with /"coronary artery disease"/. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the /"angiotensin-II type 1 receptor"/ gene polymorphisms (A1166C /"AT1R"/) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed /"coronary artery disease"/ (/"CAD"/) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C /"AT1R"/ genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C /"AT1R"/ genotypes separately were not significantly associated with the left ventricular size and function parameters in /"CAD"/ patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and /"AT1R"/ A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant /"coronary atherosclerosis"/. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | [
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12747597 | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D /"ACE"/) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D /"ACE"/ and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D /"ACE"/ and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior /"myocardial infarction"/ with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the /"ACE"/ I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | [
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12747597 | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with /"coronary artery disease"/. | The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D /"ACE"/) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed /"coronary artery disease"/ (/"CAD"/) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D /"ACE"/ and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D /"ACE"/ and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in /"CAD"/ patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the /"ACE"/ I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant /"coronary atherosclerosis"/. However, it indicates that the influence of polymorphisms may be present in specific patient populations. | [
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12750963 | Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm. | We previously performed a genome-wide linkage study of intracranial aneurysm (IA) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor 1 (FGF1), fibrillin 2 (FBN2), and lysyl oxidase gene ( LOX) lie, and evaluate associations with IA. Genomic DNAs were obtained from 172 IA patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF1 (chi(2)=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (chi(2)=16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and LOX with IA were detected in the present study. | Association of positional and functional candidate genes /"FGF1"/, FBN2, and LOX on 5q31 with /"intracranial aneurysm"/. | We previously performed a genome-wide linkage study of /"intracranial aneurysm"/ (/"IA"/) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, /"fibroblast growth factor 1"/ (/"FGF1"/), fibrillin 2 (FBN2), and lysyl oxidase gene ( LOX) lie, and evaluate associations with /"IA"/. Genomic DNAs were obtained from 172 /"IA"/ patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in /"FGF1"/, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in /"FGF1"/ (chi(2)=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in /"FGF1"/ (chi(2)=16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in /"FGF1"/ according to the linkage disequilibrium structure. No associations of FBN2 and LOX with /"IA"/ were detected in the present study. | [
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12750963 | Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm. | We previously performed a genome-wide linkage study of intracranial aneurysm (IA) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor 1 (FGF1), fibrillin 2 (FBN2), and lysyl oxidase gene ( LOX) lie, and evaluate associations with IA. Genomic DNAs were obtained from 172 IA patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF1 (chi(2)=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (chi(2)=16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and LOX with IA were detected in the present study. | Association of positional and functional candidate genes FGF1, FBN2, and /"LOX"/ on 5q31 with /"intracranial aneurysm"/. | We previously performed a genome-wide linkage study of /"intracranial aneurysm"/ (/"IA"/) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor 1 (FGF1), fibrillin 2 (FBN2), and /"lysyl oxidase gene"/ ( /"LOX"/) lie, and evaluate associations with /"IA"/. Genomic DNAs were obtained from 172 /"IA"/ patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and /"LOX"/, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF1 (chi(2)=4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (chi(2)=16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and /"LOX"/ with /"IA"/ were detected in the present study. | [
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12767526 | Association of the genetic polymorphism in cytochrome P450 (CYP) 1A1 with risk of familial prostate cancer in a Japanese population: a case-control study. | Association between genetic polymorphisms of CYP1A1 and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of CYP1A1 showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that CYP1A1 polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer. | Association of the genetic polymorphism in /"cytochrome P450 (CYP) 1A1"/ with risk of /"familial prostate cancer"/ in a Japanese population: a case-control study. | Association between genetic polymorphisms of /"CYP1A1"/ and /"familial prostate cancer"/ risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of /"CYP1A1"/ showed no significant association with /"prostate cancer"/ risk, the presence of any mutated alleles significantly /"increased prostate cancer"/ risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that /"CYP1A1"/ polymorphisms has an association with /"prostate cancer"/ risk, especially with /"progression of prostate cancer"/. | [
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