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20558149 | Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease. | The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | Complement receptor 1 polymorphisms and risk of late-onset /"Alzheimer's disease"/. | The amyloid beta-protein (/"Abeta"/)-induced complement system activation plays an important role in /"Alzheimer's disease"/ (/"AD"/). Complement receptor 1 (CR1) is thought to contribute to /"Abeta"/ clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with /"AD"/ in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset /"AD"/ (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between /"AD"/ patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | [
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20558149 | Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease. | The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | Complement receptor 1 polymorphisms and risk of late-onset /"Alzheimer's disease"/. | The amyloid beta-protein (/"Abeta"/)-induced complement system activation plays an important role in /"Alzheimer's disease"/ (/"AD"/). Complement receptor 1 (CR1) is thought to contribute to /"Abeta"/ clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with /"AD"/ in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset /"AD"/ (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between /"AD"/ patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | [
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20560254 | Heart rate variability in children with congenital sensorineural deafness. | We hypothesized that decreased sympathetic/parasympathetic balance as a result of the absence of auditory stimuli on the autonomic nervous system might be an explanation for our previous finding of lower mean heart rate in congenitally deaf children. To test our hypothesis, we obtained heart rate variability (HRV) data of 23 children with congenital sensorineural deafness from 24-hour Holter ECG recordings and compared them to data of 18 healthy children. HRV was measured by calculating time-domain and frequency-domain indexes from 24-hour recordings and from 6 hours of recordings obtained while subjects were sleeping. We additionally compared the HRV values obtained from children with and without GJB2 gene mutations. We did not find any significant difference in HRV parameters between deaf children and healthy children. There were also no significant differences in HRV parameters between deaf children with and without GJB2 mutations. We conclude that cardiac autonomic dysfunction does not seem to be present in patients with congenital sensorineural deafness. | Heart rate variability in children with /"congenital sensorineural deafness"/. | We hypothesized that decreased sympathetic/parasympathetic balance as a result of the absence of auditory stimuli on the autonomic nervous system might be an explanation for our previous finding of lower mean heart rate in congenitally deaf children. To test our hypothesis, we obtained heart rate variability (HRV) data of 23 children with /"congenital sensorineural deafness"/ from 24-hour Holter ECG recordings and compared them to data of 18 healthy children. HRV was measured by calculating time-domain and frequency-domain indexes from 24-hour recordings and from 6 hours of recordings obtained while subjects were sleeping. We additionally compared the HRV values obtained from children with and without /"GJB2"/ gene mutations. We did not find any significant difference in HRV parameters between deaf children and healthy children. There were also no significant differences in HRV parameters between deaf children with and without /"GJB2"/ mutations. We conclude that cardiac autonomic dysfunction does not seem to be present in patients with /"congenital sensorineural deafness"/. | [
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20560254 | Heart rate variability in children with congenital sensorineural deafness. | We hypothesized that decreased sympathetic/parasympathetic balance as a result of the absence of auditory stimuli on the autonomic nervous system might be an explanation for our previous finding of lower mean heart rate in congenitally deaf children. To test our hypothesis, we obtained heart rate variability (HRV) data of 23 children with congenital sensorineural deafness from 24-hour Holter ECG recordings and compared them to data of 18 healthy children. HRV was measured by calculating time-domain and frequency-domain indexes from 24-hour recordings and from 6 hours of recordings obtained while subjects were sleeping. We additionally compared the HRV values obtained from children with and without GJB2 gene mutations. We did not find any significant difference in HRV parameters between deaf children and healthy children. There were also no significant differences in HRV parameters between deaf children with and without GJB2 mutations. We conclude that cardiac autonomic dysfunction does not seem to be present in patients with congenital sensorineural deafness. | Heart rate variability in children with congenital sensorineural deafness. | We hypothesized that decreased sympathetic/parasympathetic balance as a result of the absence of auditory stimuli on the autonomic nervous system might be an explanation for our previous finding of lower mean heart rate in congenitally deaf children. To test our hypothesis, we obtained heart rate variability (HRV) data of 23 children with congenital sensorineural deafness from 24-hour Holter ECG recordings and compared them to data of 18 healthy children. HRV was measured by calculating time-domain and frequency-domain indexes from 24-hour recordings and from 6 hours of recordings obtained while subjects were sleeping. We additionally compared the HRV values obtained from children with and without /"GJB2"/ gene mutations. We did not find any significant difference in HRV parameters between deaf children and healthy children. There were also no significant differences in HRV parameters between deaf children with and without /"GJB2"/ mutations. We conclude that cardiac /"autonomic dysfunction"/ does not seem to be present in patients with congenital sensorineural deafness. | [
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20564317 | Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. | BACKGROUND: We hypothesized that genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene are associated with prostate cancer risk. METHODS: We genotyped three MTHFR polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The cancer-free controls were frequency matched to the cases by age ( 2 years), educational level, occupational status, ethnicity, and smoking status. RESULTS: We found that the MTHFR 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of prostate cancer (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of prostate cancer (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for prostate cancer (OR = 1.64; 95% CI = 0.86-2.15). Regarding prostate cancer aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade prostate cancer (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes. CONCLUSION: These data suggest that all three MTHFR polymorphisms may play a pivotal role in the developing prostate cancer. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings. | Relationship between three polymorphisms of /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/ C677T, A1298C, and G1793A) gene and risk of /"prostate cancer"/: a case-control study. | BACKGROUND: We hypothesized that genetic polymorphisms in /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) gene are associated with /"prostate cancer"/ risk. METHODS: We genotyped three /"MTHFR"/ polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The cancer-free controls were frequency matched to the cases by age ( 2 years), educational level, occupational status, ethnicity, and smoking status. RESULTS: We found that the /"MTHFR"/ 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of /"prostate cancer"/ (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of /"prostate cancer"/ (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for /"prostate cancer"/ (OR = 1.64; 95% CI = 0.86-2.15). Regarding /"prostate cancer"/ aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade /"prostate cancer"/ (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes. CONCLUSION: These data suggest that all three /"MTHFR"/ polymorphisms may play a pivotal role in the developing /"prostate cancer"/. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings. | [
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20564317 | Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. | BACKGROUND: We hypothesized that genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene are associated with prostate cancer risk. METHODS: We genotyped three MTHFR polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The cancer-free controls were frequency matched to the cases by age ( 2 years), educational level, occupational status, ethnicity, and smoking status. RESULTS: We found that the MTHFR 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of prostate cancer (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of prostate cancer (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for prostate cancer (OR = 1.64; 95% CI = 0.86-2.15). Regarding prostate cancer aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade prostate cancer (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes. CONCLUSION: These data suggest that all three MTHFR polymorphisms may play a pivotal role in the developing prostate cancer. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings. | Relationship between three polymorphisms of /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/ C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. | BACKGROUND: We hypothesized that genetic polymorphisms in /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) gene are associated with prostate cancer risk. METHODS: We genotyped three /"MTHFR"/ polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The /"cancer"/-free controls were frequency matched to the cases by age ( 2 years), educational level, occupational status, ethnicity, and smoking status. RESULTS: We found that the /"MTHFR"/ 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of prostate cancer (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of prostate cancer (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for prostate cancer (OR = 1.64; 95% CI = 0.86-2.15). Regarding prostate cancer aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade prostate cancer (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes. CONCLUSION: These data suggest that all three /"MTHFR"/ polymorphisms may play a pivotal role in the developing prostate cancer. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings. | [
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20570322 | Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and BRCA2 genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or BRCA2. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | Prevalence of /"BRCA1"/ and BRCA2 germ line mutations among women with /"carcinoma of the fallopian tube"/. | OBJECTIVES: The purpose of this study is to determine the prevalence of /"BRCA1"/ and BRCA2 mutations among a large series of women with /"carcinoma of the fallopian tube"/. METHODS: Two series of women diagnosed with /"carcinoma of the fallopian tube"/ were studied. Women identified from the Ontario Cancer Registry who were diagnosed with /"fallopian tube cancer"/ between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the /"BRCA1"/ and BRCA2 genes. RESULTS: In total, 108 patients with /"fallopian tube cancer"/ were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in /"BRCA1"/ (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with /"fallopian tube cancer"/ before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with /"fallopian tube cancer"/ have a mutation in /"BRCA1"/ or BRCA2. The highest frequencies of /"BRCA"/ mutations were seen in women with /"fallopian tube cancer"/ diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive /"fallopian tube cancer"/ should be considered candidates for genetic testing. | [
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20570322 | Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and BRCA2 genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or BRCA2. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | Prevalence of BRCA1 and /"BRCA2"/ germ line mutations among women with /"carcinoma of the fallopian tube"/. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and /"BRCA2"/ mutations among a large series of women with /"carcinoma of the fallopian tube"/. METHODS: Two series of women diagnosed with /"carcinoma of the fallopian tube"/ were studied. Women identified from the Ontario Cancer Registry who were diagnosed with /"fallopian tube cancer"/ between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and /"BRCA2"/ genes. RESULTS: In total, 108 patients with /"fallopian tube cancer"/ were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in /"BRCA2"/ (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with /"fallopian tube cancer"/ before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with /"fallopian tube cancer"/ have a mutation in BRCA1 or /"BRCA2"/. The highest frequencies of BRCA mutations were seen in women with /"fallopian tube cancer"/ diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive /"fallopian tube cancer"/ should be considered candidates for genetic testing. | [
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20570322 | Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and BRCA2 genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or BRCA2. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | Prevalence of /"BRCA1"/ and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of /"BRCA1"/ and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the /"BRCA1"/ and BRCA2 genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in /"BRCA1"/ (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of /"ovarian or breast cancer"/ was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in /"BRCA1"/ or BRCA2. The highest frequencies of /"BRCA"/ mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of /"breast or ovarian cancer"/, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | [
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20570322 | Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and BRCA2 genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or BRCA2. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | Prevalence of BRCA1 and /"BRCA2"/ germ line mutations among women with carcinoma of the fallopian tube. | OBJECTIVES: The purpose of this study is to determine the prevalence of BRCA1 and /"BRCA2"/ mutations among a large series of women with carcinoma of the fallopian tube. METHODS: Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and /"BRCA2"/ genes. RESULTS: In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in /"BRCA2"/ (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of /"breast cancer"/; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above. CONCLUSIONS: Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or /"BRCA2"/. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of /"breast cancer"/. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing. | [
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20610570 | Interleukin-6 is an essential determinant of on-time parturition in the mouse. | IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with infection-associated preterm labor. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce preterm delivery in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade. | /"Interleukin-6"/ is an essential determinant of on-time parturition in the mouse. | /"IL-6"/ abundance in amniotic fluid and uterine tissues increases in late gestation or with /"infection-associated preterm labor"/. A role in regulation of labor onset is suggested by observations that /"IL-6"/ increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether /"IL-6"/ is essential for normal parturition is unknown. To evaluate the physiological role of /"IL-6"/ in parturition in mice, we investigated the effect of /"Il6"/ null mutation on the timing of parturition and expression of genes associated with uterine activation. /"Il6"/ null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. /"Il6"/ null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce /"preterm delivery"/ in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in /"Il6"/ null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in /"Il6"/ null mutant mice. Administration of recombinant /"IL-6"/ from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that /"IL-6"/ has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade. | [
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20610570 | Interleukin-6 is an essential determinant of on-time parturition in the mouse. | IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with infection-associated preterm labor. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce preterm delivery in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade. | Interleukin-6 is an essential determinant of on-time parturition in the mouse. | IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with /"infection-associated preterm labor"/. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce /"preterm delivery"/ in wild-type mice. The characteristic late-gestation elevation in uterine expression of /"Oxtr"/ mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade. | [
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20615671 | Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia. | Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated. | Analysis of HapMap tag-SNPs in dysbindin (/"DTNBP1"/) reveals evidence of consistent association with /"schizophrenia"/. | /"Dystrobrevin binding protein 1"/ (/"DTNBP1"/), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of /"schizophrenia"/, it seems likely that glutamatergic dysfunction can lead to the development of /"schizophrenia"/. /"DTNBP1"/ is widely expressed in brain, levels are reduced in brains of /"schizophrenia"/ patients and a /"DTNBP1"/ polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no /"DTNBP1"/ polymorphism has been strongly implicated in /"schizophrenia"/ aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in /"DTNBP1"/ to investigate possible associations with /"DTNBP1"/ and /"schizophrenia"/. Four polymorphisms were found to be significantly associated with /"schizophrenia"/. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have /"schizophrenia"/ compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that /"DTNBP1"/ is a good candidate for /"schizophrenia"/ risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated. | [
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20615671 | Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia. | Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated. | Analysis of HapMap tag-SNPs in dysbindin (/"DTNBP1"/) reveals evidence of consistent association with schizophrenia. | /"Dystrobrevin binding protein 1"/ (/"DTNBP1"/), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that /"glutamatergic dysfunction"/ can lead to the development of schizophrenia. /"DTNBP1"/ is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a /"DTNBP1"/ polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no /"DTNBP1"/ polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in /"DTNBP1"/ to investigate possible associations with /"DTNBP1"/ and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that /"DTNBP1"/ is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated. | [
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20616199 | Evaluation of genetic susceptibility loci for obesity in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | Evaluation of genetic susceptibility loci for /"obesity"/ in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for /"obesity"/. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct /"obesity"/ loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and /"SH2B1"/ genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of /"obesity"/. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (/"SH2B1"/). Odds ratios for /"obesity"/ ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of /"obesity"/. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of /"obesity"/ than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | [
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20616199 | Evaluation of genetic susceptibility loci for obesity in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | Evaluation of genetic susceptibility loci for /"obesity"/ in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for /"obesity"/. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct /"obesity"/ loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the /"FTO"/, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of /"obesity"/. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for /"obesity"/ ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of /"obesity"/. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of /"obesity"/ than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | [
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20616199 | Evaluation of genetic susceptibility loci for obesity in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | Evaluation of genetic susceptibility loci for /"obesity"/ in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for /"obesity"/. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct /"obesity"/ loci. Two SNPs near the /"BAT2"/ and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of /"obesity"/. The per-allele increase in body mass index ranged from 0.16 units (/"BAT2"/) to 0.38 units (SH2B1). Odds ratios for /"obesity"/ ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for /"BAT2"/ to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of /"obesity"/. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of /"obesity"/ than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | [
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20616199 | Evaluation of genetic susceptibility loci for obesity in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | Evaluation of genetic susceptibility loci for /"obesity"/ in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for /"obesity"/. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct /"obesity"/ loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, /"SEC16B"/, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of /"obesity"/. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for /"obesity"/ ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of /"obesity"/. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of /"obesity"/ than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | [
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20616199 | Evaluation of genetic susceptibility loci for obesity in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | Evaluation of genetic susceptibility loci for /"obesity"/ in Chinese women. | Recent genome-wide association (GWA) studies have identified 18 genetic loci for /"obesity"/. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct /"obesity"/ loci. Two SNPs near the BAT2 and /"MC4R"/ genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of /"obesity"/. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for /"obesity"/ ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for /"MC4R"/. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of /"obesity"/. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of /"obesity"/ than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations. | [
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20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme /"obesity"/. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme /"obesity"/ from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 /"obese"/ case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, /"obese"/ case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for /"obesity"/, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and /"IL15"/. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of /"obesity"/ in patients with moderate /"obesity"/ and that genes impacted by large CNVs represent intriguing candidates for /"obesity"/ that warrant further study. | [
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20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme /"obesity"/. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme /"obesity"/ from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 /"obese"/ case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, /"obese"/ case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for /"obesity"/, such as a 3.3-Mb deletion disrupting /"NAP1L5"/ and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of /"obesity"/ in patients with moderate /"obesity"/ and that genes impacted by large CNVs represent intriguing candidates for /"obesity"/ that warrant further study. | [
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} | Yes |
20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme /"obesity"/. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme /"obesity"/ from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 /"obese"/ case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, /"obese"/ case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for /"obesity"/, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting /"UCP1"/ and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of /"obesity"/ in patients with moderate /"obesity"/ and that genes impacted by large CNVs represent intriguing candidates for /"obesity"/ that warrant further study. | [
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} | Yes |
20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 /"diabetes"/. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting /"NAP1L5"/ and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | [
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} | {
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} | No |
20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 /"diabetes"/. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting /"UCP1"/ and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | [
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] | {
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} | {
"begin_idx": "204",
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"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
} | No |
20622171 | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | Large copy-number variations are enriched in cases with moderate to extreme obesity. | OBJECTIVE: Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 /"diabetes"/. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects. RESEARCH DESIGN AND METHODS: Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m(2)) and 379 never-overweight control subjects (BMI <25 kg/m(2)). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with 550,000 SNP markers. The CNV calls were generated by PennCNV software. RESULTS: CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5-5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2-infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5-27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and /"IL15"/. CONCLUSIONS: Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study. | [
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},
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, /"G6PC2"/ and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), /"islet-specific glucose 6 phosphatase catalytic subunit-related protein"/ (/"G6PC2"/), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for /"type 2 diabetes"/ (/"T2D"/) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with /"T2D"/ and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, /"G6PC2"/ rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 /"T2D"/ patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both /"G6PC2"/ rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and /"G6PC2"/ rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, /"G6PC2"/ and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, G6PC2 and /"GCK"/ are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), /"glucokinase"/ (/"GCK"/) and glucokinase regulatory protein (GCKR) as candidate genes for /"type 2 diabetes"/ (/"T2D"/) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with /"T2D"/ and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, /"GCK"/ rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 /"T2D"/ patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of /"GCK"/ rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and /"GCK"/ are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in /"MTNR1B"/, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified /"melatonin receptor 1B"/ (/"MTNR1B"/), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for /"type 2 diabetes"/ (/"T2D"/) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with /"T2D"/ and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), /"MTNR1B"/ rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 /"T2D"/ patients. The G-allele of /"MTNR1B"/ rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of /"MTNR1B"/ rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of /"MTNR1B"/, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and /"glucokinase regulatory protein"/ (/"GCKR"/) as candidate genes for /"type 2 diabetes"/ (/"T2D"/) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with /"T2D"/ and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and /"GCKR"/ rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 /"T2D"/ patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with /"GCKR"/ rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, /"G6PC2"/ and GCK are associated with increased /"fasting plasma glucose"/ and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), /"islet-specific glucose 6 phosphatase catalytic subunit-related protein"/ (/"G6PC2"/), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated /"fasting plasma glucose"/ (/"FPG"/). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, /"G6PC2"/ rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both /"G6PC2"/ rs16856187 and rs478333 were associated with higher /"FPG"/ (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with /"FPG"/, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased /"FPG"/ (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and /"G6PC2"/ rs16856187 on /"FPG"/. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, /"G6PC2"/ and GCK are associated with elevated /"FPG"/ and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and /"glucokinase regulatory protein"/ (/"GCKR"/) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and /"GCKR"/ rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with /"GCKR"/ rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate /"hyperglycemia"/ in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in /"MTNR1B"/, G6PC2 and GCK are associated with increased /"fasting plasma glucose"/ and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified /"melatonin receptor 1B"/ (/"MTNR1B"/), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated /"fasting plasma glucose"/ (/"FPG"/). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), /"MTNR1B"/ rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of /"MTNR1B"/ rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher /"FPG"/ (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with /"FPG"/, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased /"FPG"/ (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of /"MTNR1B"/ rs10830963 and G6PC2 rs16856187 on /"FPG"/. CONCLUSIONS/SIGNIFICANCE: Common variants of /"MTNR1B"/, G6PC2 and GCK are associated with elevated /"FPG"/ and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20628598 | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. | BACKGROUND: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and /"glucokinase regulatory protein"/ (/"GCKR"/) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. METHODOLOGY/PRINCIPAL FINDINGS: Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and /"GCKR"/ rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with /"GCKR"/ rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. CONCLUSIONS/SIGNIFICANCE: Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and /"impaired insulin secretion"/, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. | [
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20630504 | A variant in the fibrillin-3 gene is associated with TGF-b and inhibin B levels in women with polycystic ovary syndrome. | In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) b and inhibin levels in women with polycystic ovary syndrome (PCOS), we studied 120 similarly aged women from families with PCOS and compared 40 women with PCOS who did not have A8 (A8- PCOS) with 40 women with PCOS who had A8 (A8+ PCOS) and 40 normally menstruating women who did not have either PCOS or A8 (A8- Non-PCOS). A8- PCOS is associated with higher levels of TGF-b1 compared with A8+ PCOS or A8- Non-PCOS, similar levels of TGF-b2 compared with A8+ PCOS but lower levels of TGF-b2 compared with A8- Non-PCOS, and lower levels of inhibin B and aldosterone compared with A8+ PCOS. | A variant in the /"fibrillin-3"/ gene is associated with TGF-b and inhibin B levels in women with /"polycystic ovary syndrome"/. | In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the /"fibrillin-3"/ gene and circulating transforming growth factor (TGF) b and inhibin levels in women with /"polycystic ovary syndrome"/ (/"PCOS"/), we studied 120 similarly aged women from families with /"PCOS"/ and compared 40 women with /"PCOS"/ who did not have A8 (A8- /"PCOS"/) with 40 women with /"PCOS"/ who had A8 (A8+ /"PCOS"/) and 40 normally menstruating women who did not have either /"PCOS"/ or A8 (A8- Non-/"PCOS"/). A8- /"PCOS"/ is associated with higher levels of TGF-b1 compared with A8+ /"PCOS"/ or A8- Non-/"PCOS"/, similar levels of TGF-b2 compared with A8+ /"PCOS"/ but lower levels of TGF-b2 compared with A8- Non-/"PCOS"/, and lower levels of inhibin B and aldosterone compared with A8+ /"PCOS"/. | [
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20630504 | A variant in the fibrillin-3 gene is associated with TGF-b and inhibin B levels in women with polycystic ovary syndrome. | In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) b and inhibin levels in women with polycystic ovary syndrome (PCOS), we studied 120 similarly aged women from families with PCOS and compared 40 women with PCOS who did not have A8 (A8- PCOS) with 40 women with PCOS who had A8 (A8+ PCOS) and 40 normally menstruating women who did not have either PCOS or A8 (A8- Non-PCOS). A8- PCOS is associated with higher levels of TGF-b1 compared with A8+ PCOS or A8- Non-PCOS, similar levels of TGF-b2 compared with A8+ PCOS but lower levels of TGF-b2 compared with A8- Non-PCOS, and lower levels of inhibin B and aldosterone compared with A8+ PCOS. | A variant in the fibrillin-3 gene is associated with TGF-b and inhibin B levels in women with /"polycystic ovary syndrome"/. | In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) b and inhibin levels in women with /"polycystic ovary syndrome"/ (/"PCOS"/), we studied 120 similarly aged women from families with /"PCOS"/ and compared 40 women with /"PCOS"/ who did not have A8 (/"A8- PCOS"/OS"/) with 40 women with /"PCOS"/ who had A8 (A8+ /"PCOS"/) and 40 normally menstruating women who did not have either /"PCOS"/ or A8 (A8- Non-/"PCOS"/). /"A8- PCOS"/OS"/ is associated with higher levels of TGF-b1 compared with A8+ /"PCOS"/ or A8- Non-/"PCOS"/, similar levels of TGF-b2 compared with A8+ /"PCOS"/ but lower levels of TGF-b2 compared with A8- Non-/"PCOS"/, and lower levels of inhibin B and aldosterone compared with A8+ /"PCOS"/. | [
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} | No |
20631561 | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | Endocannabinoid Pro129Thr /"FAAH"/ functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced /"weight gain"/. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced /"weight gain"/. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the /"FAAH"/ gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the /"FAAH"/ cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the /"FAAH"/ gene may predispose subjects to get a clinically meaningful /"weight gain"/ after antipsychotic exposure. | [
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20631561 | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A /"CNR1"/ polymorphism is associated with antipsychotic-induced /"weight gain"/. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced /"weight gain"/. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the /"cannabinoid receptor 1"/ (/"CNR1"/) gene, which codes the endocannabinoid /"CB1"/ receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the /"CNR1"/ 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful /"weight gain"/ after antipsychotic exposure. | [
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20631561 | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A /"CNR1"/ polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the /"cannabinoid receptor 1"/ (/"CNR1"/) gene, which codes the endocannabinoid /"CB1"/ receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white /"psychotic"/ patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the /"CNR1"/ 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | [
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20631561 | Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | Endocannabinoid Pro129Thr /"FAAH"/ functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. | Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the /"FAAH"/ gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white /"psychotic"/ patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the /"FAAH"/ cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the /"FAAH"/ gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure. | [
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20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of /"TYMS"/, MTHFR, p53 and MDR1 gene polymorphisms in patients with /"breast cancer"/ treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (/"TYMS"/), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in /"breast cancer"/ patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with /"breast cancer"/. | [
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20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of TYMS, MTHFR, p53 and /"MDR1"/ gene polymorphisms in patients with /"breast cancer"/ treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (/"MDR1"/) gene polymorphisms in /"breast cancer"/ patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; /"MDR1"/ C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with /"breast cancer"/. | [
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20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of TYMS, /"MTHFR"/, p53 and MDR1 gene polymorphisms in patients with /"breast cancer"/ treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (/"MTHFR"/), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in /"breast cancer"/ patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; /"MTHFR"/ C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. /"MTHFR"/ allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with /"breast cancer"/. | [
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} | {
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"entity_id": "D001943",
"entity_type": "Disease",
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} | Yes |
20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of TYMS, MTHFR, p53 and /"MDR1"/ gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (/"MDR1"/) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; /"MDR1"/ C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with /"toxicity"/ due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to /"toxicity"/ due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | [
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] | {
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20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of TYMS, MTHFR, /"p53"/ and MDR1 gene polymorphisms in patients with /"breast cancer"/ treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (/"p53"/) and C3435T (MDR1) gene polymorphisms in /"breast cancer"/ patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; /"p53"/ Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and /"p53"/ allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of /"p53"/ codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with /"breast cancer"/. | [
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"text_name": "breast cancer"
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20638924 | Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | Distribution of TYMS, /"MTHFR"/, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. | PURPOSE: To investigate the role of TSER (TYMS), C677T (/"MTHFR"/), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; /"MTHFR"/ C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. /"MTHFR"/ allele T and p53 allele Pro were strongly associated with /"toxicity"/ due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to /"toxicity"/ due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer. | [
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20638926 | The c.469+46_56del mutation in the homeobox MSX1 gene--a novel risk factor in breast cancer? | PURPOSE: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox MSX1 gene and breast cancer occurrence and characteristics. METHODS: The mutation was genotyped in peripheral blood lymphocytes of 200 breast cancer patients and 203 controls by single-strand conformational PCR and DNA sequencing. RESULTS: The del/del variant of the c.469+46_56del mutation increased the risk of breast cancer occurrence (OR 2.20; 95% CI 1.41-3.44, p<0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom-Richardson grading, estrogen and progesterone receptors and HER2 expression. CONCLUSIONS: The del/del genotype of the c.469+46_56del mutation in the MSX1 gene may be associated with the increased risk of breast cancer in Polish population and may be considered as an early marker in this disease. | The c.469+46_56del mutation in the homeobox /"MSX1"/ gene--a novel risk factor in /"breast cancer"/? | PURPOSE: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox /"MSX1"/ gene and /"breast cancer"/ occurrence and characteristics. METHODS: The mutation was genotyped in peripheral blood lymphocytes of 200 /"breast cancer"/ patients and 203 controls by single-strand conformational PCR and DNA sequencing. RESULTS: The del/del variant of the c.469+46_56del mutation increased the risk of /"breast cancer"/ occurrence (OR 2.20; 95% CI 1.41-3.44, p<0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom-Richardson grading, estrogen and progesterone receptors and HER2 expression. CONCLUSIONS: The del/del genotype of the c.469+46_56del mutation in the /"MSX1"/ gene may be associated with the increased risk of /"breast cancer"/ in Polish population and may be considered as an early marker in this disease. | [
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20638926 | The c.469+46_56del mutation in the homeobox MSX1 gene--a novel risk factor in breast cancer? | PURPOSE: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox MSX1 gene and breast cancer occurrence and characteristics. METHODS: The mutation was genotyped in peripheral blood lymphocytes of 200 breast cancer patients and 203 controls by single-strand conformational PCR and DNA sequencing. RESULTS: The del/del variant of the c.469+46_56del mutation increased the risk of breast cancer occurrence (OR 2.20; 95% CI 1.41-3.44, p<0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom-Richardson grading, estrogen and progesterone receptors and HER2 expression. CONCLUSIONS: The del/del genotype of the c.469+46_56del mutation in the MSX1 gene may be associated with the increased risk of breast cancer in Polish population and may be considered as an early marker in this disease. | The c.469+46_56del mutation in the homeobox MSX1 gene--a novel risk factor in /"breast cancer"/? | PURPOSE: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox MSX1 gene and /"breast cancer"/ occurrence and characteristics. METHODS: The mutation was genotyped in peripheral blood lymphocytes of 200 /"breast cancer"/ patients and 203 controls by single-strand conformational PCR and DNA sequencing. RESULTS: The del/del variant of the c.469+46_56del mutation increased the risk of /"breast cancer"/ occurrence (OR 2.20; 95% CI 1.41-3.44, p<0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom-Richardson grading, estrogen and progesterone receptors and /"HER2"/ expression. CONCLUSIONS: The del/del genotype of the c.469+46_56del mutation in the MSX1 gene may be associated with the increased risk of /"breast cancer"/ in Polish population and may be considered as an early marker in this disease. | [
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20644276 | Apolipoprotein-E genotypes and myasthenia gravis. | Autoimmune myasthenia gravis (MG) is a disorder of neuromuscular junction. Possible role of multiple genes in the development of the MG has been documented. This case-control study, studied the association of apolipoprotein E (Apo-E) alleles with MG. Anti-AChR antibody was measured using radio receptor immunoassay. Apo-E genotypes were analyzed in 120 MG patients and 120 healthy subjects. Comparison between patients with MG and controls showed no significant association with Apo-E allelic variants. However, a significant association of Apo-E4 allele with AChR-antibody positive patients was observed (P = 0.007). Also, among seropositive patients, a significant association was seen between female gender and Apo-E4 allele (P = 0.023). Our results suggest that the presence of Apo-E4 allele might influence seropositive status in patients with MG and seems an associated susceptible factor in female patients. | /"Apolipoprotein-E"/ genotypes and /"myasthenia gravis"/. | Autoimmune /"myasthenia gravis"/ (/"MG"/) is a disorder of neuromuscular junction. Possible role of multiple genes in the development of the /"MG"/ has been documented. This case-control study, studied the association of /"apolipoprotein E"/ (/"Apo-E"/) alleles with /"MG"/. Anti-AChR antibody was measured using radio receptor immunoassay. /"Apo-E"/ genotypes were analyzed in 120 /"MG"/ patients and 120 healthy subjects. Comparison between patients with /"MG"/ and controls showed no significant association with /"Apo-E"/ allelic variants. However, a significant association of /"Apo-E"/4 allele with AChR-antibody positive patients was observed (P = 0.007). Also, among seropositive patients, a significant association was seen between female gender and Apo-E4 allele (P = 0.023). Our results suggest that the presence of /"Apo-E"/4 allele might influence seropositive status in patients with /"MG"/ and seems an associated susceptible factor in female patients. | [
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20644276 | Apolipoprotein-E genotypes and myasthenia gravis. | Autoimmune myasthenia gravis (MG) is a disorder of neuromuscular junction. Possible role of multiple genes in the development of the MG has been documented. This case-control study, studied the association of apolipoprotein E (Apo-E) alleles with MG. Anti-AChR antibody was measured using radio receptor immunoassay. Apo-E genotypes were analyzed in 120 MG patients and 120 healthy subjects. Comparison between patients with MG and controls showed no significant association with Apo-E allelic variants. However, a significant association of Apo-E4 allele with AChR-antibody positive patients was observed (P = 0.007). Also, among seropositive patients, a significant association was seen between female gender and Apo-E4 allele (P = 0.023). Our results suggest that the presence of Apo-E4 allele might influence seropositive status in patients with MG and seems an associated susceptible factor in female patients. | /"Apolipoprotein-E"/ genotypes and myasthenia gravis. | Autoimmune myasthenia gravis (MG) is a /"disorder of neuromuscular junction"/. Possible role of multiple genes in the development of the MG has been documented. This case-control study, studied the association of /"apolipoprotein E"/ (/"Apo-E"/) alleles with MG. Anti-AChR antibody was measured using radio receptor immunoassay. /"Apo-E"/ genotypes were analyzed in 120 MG patients and 120 healthy subjects. Comparison between patients with MG and controls showed no significant association with /"Apo-E"/ allelic variants. However, a significant association of /"Apo-E"/4 allele with AChR-antibody positive patients was observed (P = 0.007). Also, among seropositive patients, a significant association was seen between female gender and Apo-E4 allele (P = 0.023). Our results suggest that the presence of /"Apo-E"/4 allele might influence seropositive status in patients with MG and seems an associated susceptible factor in female patients. | [
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20646601 | [Significance of K-ras detection in colorectal cancer]. | OBJECTIVE: To determine the mutation status of K-ras gene in colorectal cancer and analyze the associations between its mutation status and clinicopathological characteristics in colorectal cancer so as to select the patients likely to benefit from a targeted therapy. METHODS: A total of 208 colorectal cancer tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between K-ras mutation status and clinicopathological characteristics in colorectal cancer were analyzed. RESULTS: Of 208 cases, 91 cases of K-ras gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups. CONCLUSION: Detection of K-ras gene status in colorectal cancer will help to select the patients likely to benefit from the monoclonal antibody therapy of targeting epidermal growth factor receptor. | [Significance of /"K-ras"/ detection in /"colorectal cancer"/]. | OBJECTIVE: To determine the mutation status of /"K-ras"/ gene in /"colorectal cancer"/ and analyze the associations between its mutation status and clinicopathological characteristics in /"colorectal cancer"/ so as to select the patients likely to benefit from a targeted therapy. METHODS: A total of 208 /"colorectal cancer"/ tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between /"K-ras"/ mutation status and clinicopathological characteristics in /"colorectal cancer"/ were analyzed. RESULTS: Of 208 cases, 91 cases of /"K-ras"/ gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups. CONCLUSION: Detection of /"K-ras"/ gene status in /"colorectal cancer"/ will help to select the patients likely to benefit from the monoclonal antibody therapy of targeting epidermal growth factor receptor. | [
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20646601 | [Significance of K-ras detection in colorectal cancer]. | OBJECTIVE: To determine the mutation status of K-ras gene in colorectal cancer and analyze the associations between its mutation status and clinicopathological characteristics in colorectal cancer so as to select the patients likely to benefit from a targeted therapy. METHODS: A total of 208 colorectal cancer tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between K-ras mutation status and clinicopathological characteristics in colorectal cancer were analyzed. RESULTS: Of 208 cases, 91 cases of K-ras gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups. CONCLUSION: Detection of K-ras gene status in colorectal cancer will help to select the patients likely to benefit from the monoclonal antibody therapy of targeting epidermal growth factor receptor. | [Significance of K-ras detection in /"colorectal cancer"/]. | OBJECTIVE: To determine the mutation status of K-ras gene in /"colorectal cancer"/ and analyze the associations between its mutation status and clinicopathological characteristics in /"colorectal cancer"/ so as to select the patients likely to benefit from a targeted therapy. METHODS: A total of 208 /"colorectal cancer"/ tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between K-ras mutation status and clinicopathological characteristics in /"colorectal cancer"/ were analyzed. RESULTS: Of 208 cases, 91 cases of K-ras gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups. CONCLUSION: Detection of K-ras gene status in /"colorectal cancer"/ will help to select the patients likely to benefit from the monoclonal antibody therapy of targeting /"epidermal growth factor receptor"/. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in /"bipolar disorder"/. | Schizophrenia and /"bipolar disorder"/ are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, /"NR4A1"/ (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with /"bipolar disorder"/, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in /"bipolar disorder"/. | Schizophrenia and /"bipolar disorder"/ are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with /"bipolar disorder"/, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the NR4A3 gene with smoking behaviour in /"schizophrenia"/ and in bipolar disorder. | /"Schizophrenia"/ and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, /"NR4A1"/ (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated /"schizophrenia"/ patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in /"schizophrenia"/ and in bipolar disorder. | /"Schizophrenia"/ and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated /"schizophrenia"/ patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in /"bipolar disorder"/. | Schizophrenia and /"bipolar disorder"/ are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), /"NR4A2"/ (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with /"bipolar disorder"/, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the NR4A3 gene with smoking behaviour in /"schizophrenia"/ and in bipolar disorder. | /"Schizophrenia"/ and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), /"NR4A2"/ (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated /"schizophrenia"/ patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, /"NR4A1"/ (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20659174 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. | Replicated association of the /"NR4A3"/ gene with smoking behaviour in schizophrenia and in bipolar disorder. | Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and /"NR4A3"/ (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the /"NR4A3"/ gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the /"NR4A3"/ markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the /"NR4A3"/ SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the /"NR4A3"/ gene in nicotine addiction in patients with /"mental health disease"/, a population significantly at risk for nicotine addiction. | [
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20662556 | Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. | Interleukin-16 (IL-16), a proinflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of endometriosis. The aim of this study was to evaluate the association of IL-16 gene polymorphisms with the risk and clinical phenotypes of endometriosis in Chinese women. We analyzed rs4778889 T/C, rs11556218 T/G polymorphisms of the IL-16 gene in 230 patients with endometriosis and 203 controls in a Chinese population, using a polymerase chain reaction-high resolution melting analysis strategy and DNA sequencing methods. There was no significant difference in the genotype and allele frequencies of the rs11556218 T/G polymorphism between patients with endometriosis and controls (p>0.05). In contrast, the genotype and allele frequencies of the rs4778889 T/C polymorphism were statistically different between patients with endometriosis and controls, which resulted from a significantly increased proportion of TC heterozygote and CC homozygote carriers among patients with endometriosis (p=0.001 and 0.012, respectively); moreover, further subgroup analysis found that the genotype difference was more evident in patients with endometriosis who also experienced pain symptoms (p<0.001) than in patients without pain symptoms (p=0.625) when compared with controls. Our results suggest that the rs4778889 T/C polymorphism of the IL-16 gene may be associated with risk of endometriosis in the Chinese population, especially in patients with pain phenotype. | Association of an /"interleukin-16"/ gene polymorphism with the risk and pain phenotype of /"endometriosis"/. | /"Interleukin-16"/ (/"IL-16"/), a proinflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of /"endometriosis"/. The aim of this study was to evaluate the association of /"IL-16"/ gene polymorphisms with the risk and clinical phenotypes of /"endometriosis"/ in Chinese women. We analyzed rs4778889 T/C, rs11556218 T/G polymorphisms of the /"IL-16"/ gene in 230 patients with /"endometriosis"/ and 203 controls in a Chinese population, using a polymerase chain reaction-high resolution melting analysis strategy and DNA sequencing methods. There was no significant difference in the genotype and allele frequencies of the rs11556218 T/G polymorphism between patients with /"endometriosis"/ and controls (p>0.05). In contrast, the genotype and allele frequencies of the rs4778889 T/C polymorphism were statistically different between patients with /"endometriosis"/ and controls, which resulted from a significantly increased proportion of TC heterozygote and CC homozygote carriers among patients with /"endometriosis"/ (p=0.001 and 0.012, respectively); moreover, further subgroup analysis found that the genotype difference was more evident in patients with /"endometriosis"/ who also experienced pain symptoms (p<0.001) than in patients without pain symptoms (p=0.625) when compared with controls. Our results suggest that the rs4778889 T/C polymorphism of the /"IL-16"/ gene may be associated with risk of /"endometriosis"/ in the Chinese population, especially in patients with pain phenotype. | [
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20662556 | Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. | Interleukin-16 (IL-16), a proinflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of endometriosis. The aim of this study was to evaluate the association of IL-16 gene polymorphisms with the risk and clinical phenotypes of endometriosis in Chinese women. We analyzed rs4778889 T/C, rs11556218 T/G polymorphisms of the IL-16 gene in 230 patients with endometriosis and 203 controls in a Chinese population, using a polymerase chain reaction-high resolution melting analysis strategy and DNA sequencing methods. There was no significant difference in the genotype and allele frequencies of the rs11556218 T/G polymorphism between patients with endometriosis and controls (p>0.05). In contrast, the genotype and allele frequencies of the rs4778889 T/C polymorphism were statistically different between patients with endometriosis and controls, which resulted from a significantly increased proportion of TC heterozygote and CC homozygote carriers among patients with endometriosis (p=0.001 and 0.012, respectively); moreover, further subgroup analysis found that the genotype difference was more evident in patients with endometriosis who also experienced pain symptoms (p<0.001) than in patients without pain symptoms (p=0.625) when compared with controls. Our results suggest that the rs4778889 T/C polymorphism of the IL-16 gene may be associated with risk of endometriosis in the Chinese population, especially in patients with pain phenotype. | Association of an /"interleukin-16"/ gene polymorphism with the risk and /"pain"/ phenotype of endometriosis. | /"Interleukin-16"/ (/"IL-16"/), a proinflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of endometriosis. The aim of this study was to evaluate the association of /"IL-16"/ gene polymorphisms with the risk and clinical phenotypes of endometriosis in Chinese women. We analyzed rs4778889 T/C, rs11556218 T/G polymorphisms of the /"IL-16"/ gene in 230 patients with endometriosis and 203 controls in a Chinese population, using a polymerase chain reaction-high resolution melting analysis strategy and DNA sequencing methods. There was no significant difference in the genotype and allele frequencies of the rs11556218 T/G polymorphism between patients with endometriosis and controls (p>0.05). In contrast, the genotype and allele frequencies of the rs4778889 T/C polymorphism were statistically different between patients with endometriosis and controls, which resulted from a significantly increased proportion of TC heterozygote and CC homozygote carriers among patients with endometriosis (p=0.001 and 0.012, respectively); moreover, further subgroup analysis found that the genotype difference was more evident in patients with endometriosis who also experienced /"pain"/ symptoms (p<0.001) than in patients without /"pain"/ symptoms (p=0.625) when compared with controls. Our results suggest that the rs4778889 T/C polymorphism of the /"IL-16"/ gene may be associated with risk of endometriosis in the Chinese population, especially in patients with /"pain"/ phenotype. | [
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"text_name": "pain"
} | Yes |
20663522 | Clinical significance of polymorphism and expression of chromogranin a and endothelin-1 in prostate cancer. | PURPOSE: We investigated the clinical significance of chromogranin A and endothelin-1 polymorphism and expression in prostate cancer. MATERIALS AND METHODS: We analyzed 2 CHGA polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with prostate cancer and 316 age matched male controls. Chromogranin A and endothelin-1 expression was evaluated by immunohistochemistry in prostate specimens of 114 men with prostate cancer who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls. RESULTS: For the CHGA Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for prostate cancer than men with the CC genotype (p = 0.014). In men with prostate cancer higher chromogranin A immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that chromogranin A immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher endothelin-1 expression was observed in prostate cancers (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between chromogranin A polymorphisms, and chromogranin A and endothelin-1 expression. CONCLUSIONS: Polymorphism and expression of chromogranin A and endothelin-1 have clinical significance in prostate cancer. Chromogranin A expression was an independent predictor of biochemical failure after prostatectomy in patients with localized prostate cancer. | Clinical significance of polymorphism and expression of /"chromogranin a"/ and endothelin-1 in /"prostate cancer"/. | PURPOSE: We investigated the clinical significance of /"chromogranin A"/ and endothelin-1 polymorphism and expression in /"prostate cancer"/. MATERIALS AND METHODS: We analyzed 2 /"CHGA"/ polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with /"prostate cancer"/ and 316 age matched male controls. /"Chromogranin A"/ and endothelin-1 expression was evaluated by immunohistochemistry in prostate specimens of 114 men with /"prostate cancer"/ who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls. RESULTS: For the /"CHGA"/ Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for /"prostate cancer"/ than men with the CC genotype (p = 0.014). In men with /"prostate cancer"/ higher /"chromogranin A"/ immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that /"chromogranin A"/ immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher endothelin-1 expression was observed in /"prostate cancers"/ (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between /"chromogranin A"/ polymorphisms, and /"chromogranin A"/ and endothelin-1 expression. CONCLUSIONS: Polymorphism and expression of /"chromogranin A"/ and endothelin-1 have clinical significance in /"prostate cancer"/. /"Chromogranin A"/ expression was an independent predictor of biochemical failure after prostatectomy in patients with /"localized prostate cancer"/. | [
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"entity_id": "D011471",
"entity_type": "Disease",
"text_name": "localized prostate cancer"
} | Yes |
20663522 | Clinical significance of polymorphism and expression of chromogranin a and endothelin-1 in prostate cancer. | PURPOSE: We investigated the clinical significance of chromogranin A and endothelin-1 polymorphism and expression in prostate cancer. MATERIALS AND METHODS: We analyzed 2 CHGA polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with prostate cancer and 316 age matched male controls. Chromogranin A and endothelin-1 expression was evaluated by immunohistochemistry in prostate specimens of 114 men with prostate cancer who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls. RESULTS: For the CHGA Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for prostate cancer than men with the CC genotype (p = 0.014). In men with prostate cancer higher chromogranin A immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that chromogranin A immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher endothelin-1 expression was observed in prostate cancers (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between chromogranin A polymorphisms, and chromogranin A and endothelin-1 expression. CONCLUSIONS: Polymorphism and expression of chromogranin A and endothelin-1 have clinical significance in prostate cancer. Chromogranin A expression was an independent predictor of biochemical failure after prostatectomy in patients with localized prostate cancer. | Clinical significance of polymorphism and expression of chromogranin a and /"endothelin-1"/ in /"prostate cancer"/. | PURPOSE: We investigated the clinical significance of chromogranin A and /"endothelin-1"/ polymorphism and expression in /"prostate cancer"/. MATERIALS AND METHODS: We analyzed 2 CHGA polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with /"prostate cancer"/ and 316 age matched male controls. Chromogranin A and /"endothelin-1"/ expression was evaluated by immunohistochemistry in prostate specimens of 114 men with /"prostate cancer"/ who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls. RESULTS: For the CHGA Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for /"prostate cancer"/ than men with the CC genotype (p = 0.014). In men with /"prostate cancer"/ higher chromogranin A immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that chromogranin A immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher /"endothelin-1"/ expression was observed in /"prostate cancers"/ (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between chromogranin A polymorphisms, and chromogranin A and /"endothelin-1"/ expression. CONCLUSIONS: Polymorphism and expression of chromogranin A and /"endothelin-1"/ have clinical significance in /"prostate cancer"/. Chromogranin A expression was an independent predictor of biochemical failure after prostatectomy in patients with /"localized prostate cancer"/. | [
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20674764 | Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease. | /"Toll-like receptor 8 and 9"/ polymorphisms in /"Crimean-Congo hemorrhagic fever"/. | /"Crimean-Congo hemorrhagic fever"/ (/"CCHF"/) is an acute viral hemorrhagic fever. The clinical course and outcome of the /"CCHF infection"/ are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. /"TLR8"/ and TLR9 contribute to the recognition of viruses. We investigated frequency of /"TLR8"/ Met1Val, /"TLR8"/ -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in /"CCHF"/ patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 /"CCHF"/ patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for /"TLR8"/ Met1Val and for TLR9 -1486T/C were significantly higher in /"CCHF"/ patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of /"TLR8"/ -129G/G genotype in the fatal /"CCHF"/ patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal /"CCHF"/ patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that /"TLR8"/ Met1Val, /"TLR8"/ -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of /"CCHF disease"/. | [
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20674764 | Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease. | /"Toll-like receptor 8 and 9"/ polymorphisms in /"Crimean-Congo hemorrhagic fever"/. | /"Crimean-Congo hemorrhagic fever"/ (/"CCHF"/) is an acute viral hemorrhagic fever. The clinical course and outcome of the /"CCHF infection"/ are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and /"TLR9"/ contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, /"TLR9"/ -1486T/C and /"TLR9"/ 2458G/A polymorphisms in /"CCHF"/ patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 /"CCHF"/ patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for /"TLR9"/ -1486T/C were significantly higher in /"CCHF"/ patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal /"CCHF"/ patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of /"TLR9"/ -1486C/C genotype was significantly higher in fatal /"CCHF"/ patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and /"TLR9"/ -1486T/C polymorphisms are important on clinical course of /"CCHF disease"/. | [
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20674764 | Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease. | /"Toll-like receptor 8 and 9"/ polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute /"viral hemorrhagic fever"/. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. /"TLR8"/ and TLR9 contribute to the recognition of viruses. We investigated frequency of /"TLR8"/ Met1Val, /"TLR8"/ -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for /"TLR8"/ Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of /"TLR8"/ -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that /"TLR8"/ Met1Val, /"TLR8"/ -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease. | [
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20674764 | Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease. | /"Toll-like receptor 8 and 9"/ polymorphisms in Crimean-Congo hemorrhagic fever. | Crimean-Congo hemorrhagic fever (CCHF) is an acute /"viral hemorrhagic fever"/. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and /"TLR9"/ contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, /"TLR9"/ -1486T/C and /"TLR9"/ 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for /"TLR9"/ -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of /"TLR9"/ -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and /"TLR9"/ -1486T/C polymorphisms are important on clinical course of CCHF disease. | [
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20683028 | Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population. | BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated. PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). RESULTS AND CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004). | Combined effect of /"CYP1B1"/ codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to /"breast cancer"/ in the Turkish population. | BACKGROUND: /"Breast cancer"/ (/"BC"/), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. /"Cytochrome P450 1B1"/ (/"CYP1B1"/) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, /"CYP1B1"/ also hyroxylates 17-beta oestradiol. /"CYP1B1"/*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated. PATIENTS AND METHODS: Sixty Turkish female /"BC"/ patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). RESULTS AND CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with /"breast cancer"/ patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). /"Breast cancer"/ patients were detected to posses more /"CYP1B1"/*3 mutant alleles than the controls (p=0.043). The combined effect of /"CYP1B1"/*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for /"breast cancer"/ in patients in this study (p=0.004). | [
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20683028 | Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population. | BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated. PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). RESULTS AND CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004). | Combined effect of CYP1B1 codon 432 polymorphism and /"N-acetyltransferase 2"/ slow acetylator phenotypes in relation to /"breast cancer"/ in the Turkish population. | BACKGROUND: /"Breast cancer"/ (/"BC"/), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and /"N-acetyltransferase2"/ (/"NAT2"/) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of /"NAT2"/ were investigated. PATIENTS AND METHODS: Sixty Turkish female /"BC"/ patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). RESULTS AND CONCLUSION: The distribution of /"NAT2"/ activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of /"NAT2"/, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the /"NAT2"/*5 alelle was more statistically correlated with /"breast cancer"/ patients rather than the controls (p=0.02). Moreover, /"NAT2"/*5B was the most frequent haplotype of the /"NAT2"/*5 family (p=0.000). /"Breast cancer"/ patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and /"NAT2"/ slow acetylator genotype contributed to an increased risk for /"breast cancer"/ in patients in this study (p=0.004). | [
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20691689 | Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. | BACKGROUND _ AIMS: Sodium chenodeoxycholate (CDC) accelerates colonic transit in health. Our aim was to examine pharmacodynamics (colonic transit, bowel function) and pharmacogenetics of CDC in constipation-predominant irritable bowel syndrome (IBS-C). METHODS: In a double-blind placebo-controlled study, 36 female patients with IBS-C were randomized to treatment with delayed-release oral formulations of placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and colonic transit, stool characteristics, and associations of transit with fasting serum 7aC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator of bile acid synthesis) levels. Candidate genetic polymorphisms involved in regulation of bile acid synthesis were analyzed in the 36 patients with IBS-C and 57 healthy volunteers to assess genetic influence on effects of CDC on transit. RESULTS: Overall colonic transit and ascending colon emptying (AC t( )) were significantly accelerated in the CDC group compared with placebo (P = .005 and P = .028, respectively). Looser stool consistency (P = .003), increased stool frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC compared with placebo. The most common side effect was lower abdominal cramping/pain (P = .01). Fasting serum 7aC4 (but not FGF19) was positively associated with colonic transit (r(s) = 0.749, P = .003, placebo group). Genetic variation in FGFR4 was associated with AC t( ) in response to CDC (uncorrected P = .015); aKlothob variant showed a gene-by-treatment interaction based on patient subgroup (uncorrected P = .0088). CONCLUSIONS: CDC accelerates colonic transit and improves bowel function in female patients with IBS-C. The rate of bile acid synthesis influences colonic transit. Genetic variation in negative feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration of colonic transit. | Chenodeoxycholate in females with /"irritable bowel syndrome-constipation"/: a pharmacodynamic and pharmacogenetic analysis. | BACKGROUND _ AIMS: Sodium chenodeoxycholate (CDC) accelerates colonic transit in health. Our aim was to examine pharmacodynamics (colonic transit, bowel function) and pharmacogenetics of CDC in constipation-predominant /"irritable bowel syndrome"/ (IBS-C). METHODS: In a double-blind placebo-controlled study, 36 female patients with IBS-C were randomized to treatment with delayed-release oral formulations of placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and colonic transit, stool characteristics, and associations of transit with fasting serum 7aC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator of bile acid synthesis) levels. Candidate genetic polymorphisms involved in regulation of bile acid synthesis were analyzed in the 36 patients with IBS-C and 57 healthy volunteers to assess genetic influence on effects of CDC on transit. RESULTS: Overall colonic transit and ascending colon emptying (AC t( )) were significantly accelerated in the CDC group compared with placebo (P = .005 and P = .028, respectively). Looser stool consistency (P = .003), increased stool frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC compared with placebo. The most common side effect was lower abdominal cramping/pain (P = .01). Fasting serum 7aC4 (but not FGF19) was positively associated with colonic transit (r(s) = 0.749, P = .003, placebo group). Genetic variation in /"FGFR4"/ was associated with AC t( ) in response to CDC (uncorrected P = .015); aKlothob variant showed a gene-by-treatment interaction based on patient subgroup (uncorrected P = .0088). CONCLUSIONS: CDC accelerates colonic transit and improves bowel function in female patients with IBS-C. The rate of bile acid synthesis influences colonic transit. Genetic variation in negative feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration of colonic transit. | [
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20691689 | Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. | BACKGROUND _ AIMS: Sodium chenodeoxycholate (CDC) accelerates colonic transit in health. Our aim was to examine pharmacodynamics (colonic transit, bowel function) and pharmacogenetics of CDC in constipation-predominant irritable bowel syndrome (IBS-C). METHODS: In a double-blind placebo-controlled study, 36 female patients with IBS-C were randomized to treatment with delayed-release oral formulations of placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and colonic transit, stool characteristics, and associations of transit with fasting serum 7aC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator of bile acid synthesis) levels. Candidate genetic polymorphisms involved in regulation of bile acid synthesis were analyzed in the 36 patients with IBS-C and 57 healthy volunteers to assess genetic influence on effects of CDC on transit. RESULTS: Overall colonic transit and ascending colon emptying (AC t( )) were significantly accelerated in the CDC group compared with placebo (P = .005 and P = .028, respectively). Looser stool consistency (P = .003), increased stool frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC compared with placebo. The most common side effect was lower abdominal cramping/pain (P = .01). Fasting serum 7aC4 (but not FGF19) was positively associated with colonic transit (r(s) = 0.749, P = .003, placebo group). Genetic variation in FGFR4 was associated with AC t( ) in response to CDC (uncorrected P = .015); aKlothob variant showed a gene-by-treatment interaction based on patient subgroup (uncorrected P = .0088). CONCLUSIONS: CDC accelerates colonic transit and improves bowel function in female patients with IBS-C. The rate of bile acid synthesis influences colonic transit. Genetic variation in negative feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration of colonic transit. | Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. | BACKGROUND _ AIMS: Sodium chenodeoxycholate (CDC) accelerates colonic transit in health. Our aim was to examine pharmacodynamics (colonic transit, bowel function) and pharmacogenetics of CDC in constipation-predominant irritable bowel syndrome (/"IBS-C"/). METHODS: In a double-blind placebo-controlled study, 36 female patients with /"IBS-C"/ were randomized to treatment with delayed-release oral formulations of placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and colonic transit, stool characteristics, and associations of transit with fasting serum 7aC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator of bile acid synthesis) levels. Candidate genetic polymorphisms involved in regulation of bile acid synthesis were analyzed in the 36 patients with /"IBS-C"/ and 57 healthy volunteers to assess genetic influence on effects of CDC on transit. RESULTS: Overall colonic transit and ascending colon emptying (AC t( )) were significantly accelerated in the CDC group compared with placebo (P = .005 and P = .028, respectively). Looser stool consistency (P = .003), increased stool frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC compared with placebo. The most common side effect was lower abdominal cramping/pain (P = .01). Fasting serum 7aC4 (but not FGF19) was positively associated with colonic transit (r(s) = 0.749, P = .003, placebo group). Genetic variation in /"FGFR4"/ was associated with AC t( ) in response to CDC (uncorrected P = .015); aKlothob variant showed a gene-by-treatment interaction based on patient subgroup (uncorrected P = .0088). CONCLUSIONS: CDC accelerates colonic transit and improves bowel function in female patients with /"IBS-C"/. The rate of bile acid synthesis influences colonic transit. Genetic variation in negative feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration of colonic transit. | [
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20699619 | Expression of genes involved in lipid metabolism in men with impaired glucose tolerance: impact of insulin stimulation and weight loss. | BACKGROUND: The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of weight loss. METHODS: Seven IGT men and 5 men with normal glucose tolerance (NGT), comparable in terms of age and BMI, participated in the study. The 5 IGT men followed a 12-week weight loss program. Muscle biopsies were taken and the expression of 6 genes was investigated. RESULTS: Subjects had a reduction of 15.5 4.3 kg in body weight. Baseline gene expression was not different between NGT and IGT men. After a hyperinsulinemic clamp, there was an overall upregulation of PGC1a, SREBP-1c, SREBP-2, and ACC-2. The upregulation of SREBP-2 was more pronounced in IGT men (p = 0.049). Weight loss significantly increased insulin sensitivity by 71%, which was not reflected in altered gene expression profiles. CONCLUSIONS: SREBP-2 shows altered insulin responsiveness in IGT men compared with NGT men, while there were no differences in basal gene expression. | Expression of genes involved in lipid metabolism in men with impaired glucose tolerance: impact of insulin stimulation and weight loss. | BACKGROUND: The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of weight loss. METHODS: Seven IGT men and 5 men with normal glucose tolerance (NGT), comparable in terms of age and BMI, participated in the study. The 5 IGT men followed a 12-week weight loss program. Muscle biopsies were taken and the expression of 6 genes was investigated. RESULTS: Subjects had a reduction of 15.5 4.3 kg in body weight. Baseline gene expression was not different between NGT and IGT men. After a hyperinsulinemic clamp, there was an overall upregulation of PGC1a, SREBP-1c, /"SREBP-2"/, and ACC-2. The upregulation of /"SREBP-2"/ was more pronounced in IGT men (p = 0.049). Weight loss significantly /"increased insulin sensitivity"/ by 71%, which was not reflected in altered gene expression profiles. CONCLUSIONS: /"SREBP-2"/ shows altered insulin responsiveness in IGT men compared with NGT men, while there were no differences in basal gene expression. | [
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20699619 | Expression of genes involved in lipid metabolism in men with impaired glucose tolerance: impact of insulin stimulation and weight loss. | BACKGROUND: The impaired glucose tolerance (IGT) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of weight loss. METHODS: Seven IGT men and 5 men with normal glucose tolerance (NGT), comparable in terms of age and BMI, participated in the study. The 5 IGT men followed a 12-week weight loss program. Muscle biopsies were taken and the expression of 6 genes was investigated. RESULTS: Subjects had a reduction of 15.5 4.3 kg in body weight. Baseline gene expression was not different between NGT and IGT men. After a hyperinsulinemic clamp, there was an overall upregulation of PGC1a, SREBP-1c, SREBP-2, and ACC-2. The upregulation of SREBP-2 was more pronounced in IGT men (p = 0.049). Weight loss significantly increased insulin sensitivity by 71%, which was not reflected in altered gene expression profiles. CONCLUSIONS: SREBP-2 shows altered insulin responsiveness in IGT men compared with NGT men, while there were no differences in basal gene expression. | Expression of genes involved in lipid metabolism in men with /"impaired glucose tolerance"/: impact of insulin stimulation and weight loss. | BACKGROUND: The /"impaired glucose tolerance"/ (/"IGT"/) state is characterized by insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this reduced insulin sensitivity. The aim of this study was to investigate whether the prediabetic state is accompanied by changes in the expression of genes involved in FA handling during fasting and in insulin-mediated conditions and to study the impact of weight loss. METHODS: Seven /"IGT"/ men and 5 men with normal glucose tolerance (NGT), comparable in terms of age and BMI, participated in the study. The 5 /"IGT"/ men followed a 12-week weight loss program. Muscle biopsies were taken and the expression of 6 genes was investigated. RESULTS: Subjects had a reduction of 15.5 4.3 kg in body weight. Baseline gene expression was not different between NGT and /"IGT"/ men. After a hyperinsulinemic clamp, there was an overall upregulation of PGC1a, SREBP-1c, /"SREBP-2"/, and ACC-2. The upregulation of /"SREBP-2"/ was more pronounced in /"IGT"/ men (p = 0.049). Weight loss significantly increased insulin sensitivity by 71%, which was not reflected in altered gene expression profiles. CONCLUSIONS: /"SREBP-2"/ shows altered insulin responsiveness in /"IGT"/ men compared with NGT men, while there were no differences in basal gene expression. | [
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20703234 | Association of the angiotensin II type I receptor gene +1166 A>C polymorphism with hypertension risk: evidence from a meta-analysis of 16474 subjects. | Mounting evidence suggests the potential susceptibility of individuals with a mutation in the angiotensin II type I receptor (AT1R) gene to hypertension. One polymorphism, +1166 A>C, has been extensively studied, but the results have often been irreproducible. We therefore aimed to meta-analyze all available case-control studies from the English language literature to explore the association of this polymorphism with hypertension. A total of 22 studies with 24 populations involving 8249 patients and 8225 controls were identified as of 25 February 2010. A random-effects model was performed regardless of the between-study heterogeneity. The study quality was assessed in duplicate. The data were analyzed using RevMan software (version 5.0.23). Overall, the presence of the +1166 C allele significantly conferred an increased risk of hypertension (odds ratio (OR)=1.14; 95% confidence interval, 1.00-1.30; P=0.05). Under the assumption of three genetic modes of inheritance, an elevated hypertension risk was observed for each comparison (codominant: AC vs. AA, OR=1.10 (P=0.20) and CC vs. AA, OR=1.21 (P=0.36); dominant: OR=1.13 (P=0.09); recessive: OR=1.21 (P=0.36)). Upon stratification by study design, more obvious associations were observed for the population-based design, whereas there were no changes in direction and only slight changes in magnitude upon stratification by sample size and geographical area. No publication biases were indicated by the fail-safe number. Our study pooled previous findings and showed that the AT1R +1166 C allele conferred an increased risk of hypertension. We suggest that confirmation in a large, well-designed study or from functional aspects of this polymorphism is critical. | Association of the angiotensin II type I receptor gene +1166 A>C polymorphism with /"hypertension"/ risk: evidence from a meta-analysis of 16474 subjects. | Mounting evidence suggests the potential susceptibility of individuals with a mutation in the angiotensin II type I receptor (/"AT1R"/) gene to /"hypertension"/. One polymorphism, +1166 A>C, has been extensively studied, but the results have often been irreproducible. We therefore aimed to meta-analyze all available case-control studies from the English language literature to explore the association of this polymorphism with /"hypertension"/. A total of 22 studies with 24 populations involving 8249 patients and 8225 controls were identified as of 25 February 2010. A random-effects model was performed regardless of the between-study heterogeneity. The study quality was assessed in duplicate. The data were analyzed using RevMan software (version 5.0.23). Overall, the presence of the +1166 C allele significantly conferred an increased risk of /"hypertension"/ (odds ratio (OR)=1.14; 95% confidence interval, 1.00-1.30; P=0.05). Under the assumption of three genetic modes of inheritance, an elevated /"hypertension"/ risk was observed for each comparison (codominant: AC vs. AA, OR=1.10 (P=0.20) and CC vs. AA, OR=1.21 (P=0.36); dominant: OR=1.13 (P=0.09); recessive: OR=1.21 (P=0.36)). Upon stratification by study design, more obvious associations were observed for the population-based design, whereas there were no changes in direction and only slight changes in magnitude upon stratification by sample size and geographical area. No publication biases were indicated by the fail-safe number. Our study pooled previous findings and showed that the /"AT1R"/ +1166 C allele conferred an increased risk of /"hypertension"/. We suggest that confirmation in a large, well-designed study or from functional aspects of this polymorphism is critical. | [
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20709820 | Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema. | RATIONALE: chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. OBJECTIVES: to identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. METHODS: we performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS: we identified association of a single-nucleotide polymorphism in BICD1 with the presence or absence of emphysema (P = 5.2 10(-7) with at least mild emphysema vs. control subjects; P = 4.8 10(-8) with moderate and more severe emphysema vs. control subjects). CONCLUSIONS: our study suggests that genetic variants in BICD1 are associated with qualitative emphysema in COPD. Variants in BICD1 are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552). | Genome-wide association study identifies /"BICD1"/ as a susceptibility gene for /"emphysema"/. | RATIONALE: chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as /"emphysema"/, may be influenced by specific genetic factors. OBJECTIVES: to identify genetic determinants of /"emphysema"/ assessed through high-resolution chest computed tomography in individuals with COPD. METHODS: we performed a genome-wide association study (GWAS) of /"emphysema"/ determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of /"emphysema"/ determined by radiologist assessment in two of the three cohorts and a quantitative /"emphysema"/ trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS: we identified association of a single-nucleotide polymorphism in /"BICD1"/ with the presence or absence of /"emphysema"/ (P = 5.2 10(-7) with at least mild /"emphysema"/ vs. control subjects; P = 4.8 10(-8) with moderate and more severe /"emphysema"/ vs. control subjects). CONCLUSIONS: our study suggests that genetic variants in /"BICD1"/ are associated with qualitative /"emphysema"/ in COPD. Variants in /"BICD1"/ are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of /"emphysema"/. Clinical trial registered with www.clinicaltrials.gov (NCT00292552). | [
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20709820 | Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema. | RATIONALE: chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. OBJECTIVES: to identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. METHODS: we performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS: we identified association of a single-nucleotide polymorphism in BICD1 with the presence or absence of emphysema (P = 5.2 10(-7) with at least mild emphysema vs. control subjects; P = 4.8 10(-8) with moderate and more severe emphysema vs. control subjects). CONCLUSIONS: our study suggests that genetic variants in BICD1 are associated with qualitative emphysema in COPD. Variants in BICD1 are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552). | Genome-wide association study identifies /"BICD1"/ as a susceptibility gene for emphysema. | RATIONALE: chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. /"Pulmonary emphysema"/ is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. OBJECTIVES: to identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. METHODS: we performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS: we identified association of a single-nucleotide polymorphism in /"BICD1"/ with the presence or absence of emphysema (P = 5.2 10(-7) with at least mild emphysema vs. control subjects; P = 4.8 10(-8) with moderate and more severe emphysema vs. control subjects). CONCLUSIONS: our study suggests that genetic variants in /"BICD1"/ are associated with qualitative emphysema in COPD. Variants in /"BICD1"/ are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552). | [
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20722399 | Activation of Nrf2 by microcystin-LR provides advantages for liver cancer cell growth. | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of Nrf2 contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of Nrf2 activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Hep3B cells with MC-LR resulted in significant increases in Nrf2-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate Nrf2. Nrf2 knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of Nrf2 in cancer cells promotes liver cancer cell growth and suggest a positive role of Nrf2 in tumorigenesis. | Activation of /"Nrf2"/ by microcystin-LR provides advantages for /"liver cancer"/ cell growth. | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor /"nuclear factor erythroid 2-related factor 2"/ (/"Nrf2"/) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of /"Nrf2"/ contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of /"Nrf2"/ activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Hep3B cells with MC-LR resulted in significant increases in /"Nrf2"/-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate /"Nrf2"/. /"Nrf2"/ knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of /"Nrf2"/ in cancer cells promotes /"liver cancer"/ cell growth and suggest a positive role of /"Nrf2"/ in tumorigenesis. | [
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20722399 | Activation of Nrf2 by microcystin-LR provides advantages for liver cancer cell growth. | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of Nrf2 contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of Nrf2 activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Hep3B cells with MC-LR resulted in significant increases in Nrf2-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate Nrf2. Nrf2 knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of Nrf2 in cancer cells promotes liver cancer cell growth and suggest a positive role of Nrf2 in tumorigenesis. | Activation of /"Nrf2"/ by microcystin-LR provides advantages for liver cancer cell growth. | Microcystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor /"nuclear factor erythroid 2-related factor 2"/ (/"Nrf2"/) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of /"Nrf2"/ contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of /"Nrf2"/ activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Hep3B cells with MC-LR resulted in significant increases in /"Nrf2"/-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate /"Nrf2"/. /"Nrf2"/ knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of /"Nrf2"/ in /"cancer"/ cells promotes liver cancer cell growth and suggest a positive role of /"Nrf2"/ in tumorigenesis. | [
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20724655 | Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study. | Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in apolipoprotein B (APOB), an essential core of triglyceride-rich lipoprotein formation, may account for some of the inter-individual differences observed in triglyceride (TG) response to fenofibrate treatment. Participants (N = 958) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a three-week intervention with fenofibrate 160 mg/day. Associations of four APOB gene single nucleotide polymorphisms (SNP) (rs934197, rs693, rs676210, and rs1042031) were tested for association with the TG response to fenofibrate using a mixed growth curve model where the familial structure was modeled as a random effect and cardiovascular risk factors were included as covariates. Three of these four SNPs changed the amino acid sequence of APOB, and the fourth was in the promoter region. TG response to fenofibrate treatment was associated with one APOB SNP, rs676210 (Pro2739Leu), such that participants with the TT genotype of rs676210 had greater TG lowering than those with the CC genotype (additive model, P = 0.0017). We conclude the rs676210 variant may identify individuals who respond best to fenofibrate for TG reduction. | /"Apolipoprotein B"/ genetic variants modify the response to fenofibrate: a GOLDN study. | /"Hypertriglyceridemia"/, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat /"hypertriglyceridemia"/, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in /"apolipoprotein B"/ (/"APOB"/), an essential core of triglyceride-rich lipoprotein formation, may account for some of the inter-individual differences observed in triglyceride (TG) response to fenofibrate treatment. Participants (N = 958) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a three-week intervention with fenofibrate 160 mg/day. Associations of four /"APOB"/ gene single nucleotide polymorphisms (SNP) (rs934197, rs693, rs676210, and rs1042031) were tested for association with the TG response to fenofibrate using a mixed growth curve model where the familial structure was modeled as a random effect and cardiovascular risk factors were included as covariates. Three of these four SNPs changed the amino acid sequence of /"APOB"/, and the fourth was in the promoter region. TG response to fenofibrate treatment was associated with one /"APOB"/ SNP, rs676210 (Pro2739Leu), such that participants with the TT genotype of rs676210 had greater TG lowering than those with the CC genotype (additive model, P = 0.0017). We conclude the rs676210 variant may identify individuals who respond best to fenofibrate for TG reduction. | [
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20724655 | Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study. | Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in apolipoprotein B (APOB), an essential core of triglyceride-rich lipoprotein formation, may account for some of the inter-individual differences observed in triglyceride (TG) response to fenofibrate treatment. Participants (N = 958) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a three-week intervention with fenofibrate 160 mg/day. Associations of four APOB gene single nucleotide polymorphisms (SNP) (rs934197, rs693, rs676210, and rs1042031) were tested for association with the TG response to fenofibrate using a mixed growth curve model where the familial structure was modeled as a random effect and cardiovascular risk factors were included as covariates. Three of these four SNPs changed the amino acid sequence of APOB, and the fourth was in the promoter region. TG response to fenofibrate treatment was associated with one APOB SNP, rs676210 (Pro2739Leu), such that participants with the TT genotype of rs676210 had greater TG lowering than those with the CC genotype (additive model, P = 0.0017). We conclude the rs676210 variant may identify individuals who respond best to fenofibrate for TG reduction. | /"Apolipoprotein B"/ genetic variants modify the response to fenofibrate: a GOLDN study. | Hypertriglyceridemia, defined as a /"triglyceride"/ measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in /"apolipoprotein B"/ (/"APOB"/), an essential core of /"triglyceride"/-rich lipoprotein formation, may account for some of the inter-individual differences observed in /"triglyceride"/ (/"TG"/) response to fenofibrate treatment. Participants (N = 958) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a three-week intervention with fenofibrate 160 mg/day. Associations of four /"APOB"/ gene single nucleotide polymorphisms (SNP) (rs934197, rs693, rs676210, and rs1042031) were tested for association with the /"TG"/ response to fenofibrate using a mixed growth curve model where the familial structure was modeled as a random effect and cardiovascular risk factors were included as covariates. Three of these four SNPs changed the amino acid sequence of /"APOB"/, and the fourth was in the promoter region. /"TG"/ response to fenofibrate treatment was associated with one /"APOB"/ SNP, rs676210 (Pro2739Leu), such that participants with the TT genotype of rs676210 had greater /"TG"/ lowering than those with the CC genotype (additive model, P = 0.0017). We conclude the rs676210 variant may identify individuals who respond best to fenofibrate for /"TG"/ reduction. | [
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20724907 | Genetic polymorphisms in apolipoprotein E and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for AD, whereas the leu allele of GPX1 is a possible risk factor for the disease. | Genetic polymorphisms in /"apolipoprotein E"/ and glutathione peroxidase 1 genes in the Ecuadorian population affected with /"Alzheimer's disease"/. | INTRODUCTION: The main objective of this study is to determine the prevalence of /"apolipoprotein E"/ (/"Apo E"/) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of /"Alzheimer disease"/ (/"AD"/) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with /"AD"/ and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of /"Apo E"/. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: /"Apo E"/ is not a risk factor, nor a protective one for /"AD"/, whereas the leu allele of GPX1 is a possible risk factor for the disease. | [
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} | Yes |
20724907 | Genetic polymorphisms in apolipoprotein E and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for AD, whereas the leu allele of GPX1 is a possible risk factor for the disease. | Genetic polymorphisms in apolipoprotein E and /"glutathione peroxidase 1"/ genes in the Ecuadorian population affected with /"Alzheimer's disease"/. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and /"glutathione peroxidase 1"/ (/"GPX1"/) polymorphisms and their influence on the development of /"Alzheimer disease"/ (/"AD"/) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with /"AD"/ and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The /"GPX1"/ gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for /"AD"/, whereas the leu allele of /"GPX1"/ is a possible risk factor for the disease. | [
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20724907 | Genetic polymorphisms in apolipoprotein E and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for AD, whereas the leu allele of GPX1 is a possible risk factor for the disease. | Genetic polymorphisms in apolipoprotein E and /"glutathione peroxidase 1"/ genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and /"glutathione peroxidase 1"/ (/"GPX1"/) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and /"dementia"/. The control group (n = 39) comprised elderly adults who have not been diagnosed with /"dementia"/ and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The /"GPX1"/ gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for AD, whereas the leu allele of /"GPX1"/ is a possible risk factor for the disease. | [
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20724907 | Genetic polymorphisms in apolipoprotein E and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of apolipoprotein E (Apo E) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and dementia. The control group (n = 39) comprised elderly adults who have not been diagnosed with dementia and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of Apo E. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: Apo E is not a risk factor, nor a protective one for AD, whereas the leu allele of GPX1 is a possible risk factor for the disease. | Genetic polymorphisms in /"apolipoprotein E"/ and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. | INTRODUCTION: The main objective of this study is to determine the prevalence of /"apolipoprotein E"/ (/"Apo E"/) and glutathione peroxidase 1 (GPX1) polymorphisms and their influence on the development of Alzheimer disease (AD) in the Ecuadorian population. METHODS: The authors performed an analytic transversal case-control study. The study group (n = 39) consisted of patients with AD and /"dementia"/. The control group (n = 39) comprised elderly adults who have not been diagnosed with /"dementia"/ and have the same age and education as the study group. Their inclusion period was from 2007 to 2008. Later on, after obtaining informed consent and after finishing a structural interview; the next step forward was to collect blood and extract DNA by standardized protocols. Besides, the authors performed polymerase chain reaction-restriction fragment length polymorphism technique to determine the genotype of each individual. RESULTS: The authors found a positive association between 4 and 2 alleles of /"Apo E"/. The GPX1 gene shows an association of leu allele, whereas pro allele shows a negative association. The odds ratio test shows no significant relative risk. CONCLUSIONS: /"Apo E"/ is not a risk factor, nor a protective one for AD, whereas the leu allele of GPX1 is a possible risk factor for the disease. | [
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20799519 | Genetic variants of the drug-metabolizing enzyme CYP2D6 in Puerto Rican psychiatry patients: a preliminary report and potential implications for breast cancer patients. | BACKGROUND: The CYP2D6 liver enzyme, which metabolizes 25-30% of common medications, is highly polymorphic. Existing studies of Hispanics have focused on Mexicans and Mexican-Americans. The goal of the study was to identify the CYP2D6 alleles associated with reduced or negligible activities present in the Puerto Rican population. METHODS: The study cohort comprised 40 Puerto Rican psychiatric patients referred because of suspected intolerance of drugs metabolized by CYP2D6, and five subjects without suspected adverse responses to these drugs. All subjects had both parents and all grandparents born in Puerto Rico. Genomic DNA was queried for 27 CYP2D6 alleles using the Roche AmpliChip P450 test. RESULTS: A total of 12 alleles were identified. The most common alleles were CYP2D6*1 > *2 > *4 > *41. The inactive alleles were *4 > * 5 > * 31 >*40; reduced activity alleles were *10 >* 17 > *9* = *29; active alleles were *1 > *2 > *35. Two subjects carried the rare *31 allele. Only one subject carried two non-functional alleles (CYP2D6*5/*40), and was predicted to be a poor metabolizer. CONCLUSIONS: Any conclusions should be interpreted with caution given the small population sample investigated. Nonetheless, our findings strongly suggest that Puerto Ricans exhibit distinct CYP2D6 allele frequencies and harbor a non-functional allele that is rare or absent in other populations and are highly valuable for the emerging practice of Personalized Medicine in admixed populations like Puerto Ricans. | Genetic variants of the drug-metabolizing enzyme /"CYP2D6"/ in Puerto Rican psychiatry patients: a preliminary report and potential implications for /"breast cancer"/ patients. | BACKGROUND: The /"CYP2D6"/ liver enzyme, which metabolizes 25-30% of common medications, is highly polymorphic. Existing studies of Hispanics have focused on Mexicans and Mexican-Americans. The goal of the study was to identify the /"CYP2D6"/ alleles associated with reduced or negligible activities present in the Puerto Rican population. METHODS: The study cohort comprised 40 Puerto Rican psychiatric patients referred because of suspected intolerance of drugs metabolized by /"CYP2D6"/, and five subjects without suspected adverse responses to these drugs. All subjects had both parents and all grandparents born in Puerto Rico. Genomic DNA was queried for 27 /"CYP2D6"/ alleles using the Roche AmpliChip P450 test. RESULTS: A total of 12 alleles were identified. The most common alleles were /"CYP2D6"/*1 > *2 > *4 > *41. The inactive alleles were *4 > * 5 > * 31 >*40; reduced activity alleles were *10 >* 17 > *9* = *29; active alleles were *1 > *2 > *35. Two subjects carried the rare *31 allele. Only one subject carried two non-functional alleles (/"CYP2D6"/*5/*40), and was predicted to be a poor metabolizer. CONCLUSIONS: Any conclusions should be interpreted with caution given the small population sample investigated. Nonetheless, our findings strongly suggest that Puerto Ricans exhibit distinct /"CYP2D6"/ allele frequencies and harbor a non-functional allele that is rare or absent in other populations and are highly valuable for the emerging practice of Personalized Medicine in admixed populations like Puerto Ricans. | [
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20799519 | Genetic variants of the drug-metabolizing enzyme CYP2D6 in Puerto Rican psychiatry patients: a preliminary report and potential implications for breast cancer patients. | BACKGROUND: The CYP2D6 liver enzyme, which metabolizes 25-30% of common medications, is highly polymorphic. Existing studies of Hispanics have focused on Mexicans and Mexican-Americans. The goal of the study was to identify the CYP2D6 alleles associated with reduced or negligible activities present in the Puerto Rican population. METHODS: The study cohort comprised 40 Puerto Rican psychiatric patients referred because of suspected intolerance of drugs metabolized by CYP2D6, and five subjects without suspected adverse responses to these drugs. All subjects had both parents and all grandparents born in Puerto Rico. Genomic DNA was queried for 27 CYP2D6 alleles using the Roche AmpliChip P450 test. RESULTS: A total of 12 alleles were identified. The most common alleles were CYP2D6*1 > *2 > *4 > *41. The inactive alleles were *4 > * 5 > * 31 >*40; reduced activity alleles were *10 >* 17 > *9* = *29; active alleles were *1 > *2 > *35. Two subjects carried the rare *31 allele. Only one subject carried two non-functional alleles (CYP2D6*5/*40), and was predicted to be a poor metabolizer. CONCLUSIONS: Any conclusions should be interpreted with caution given the small population sample investigated. Nonetheless, our findings strongly suggest that Puerto Ricans exhibit distinct CYP2D6 allele frequencies and harbor a non-functional allele that is rare or absent in other populations and are highly valuable for the emerging practice of Personalized Medicine in admixed populations like Puerto Ricans. | Genetic variants of the drug-metabolizing enzyme /"CYP2D6"/ in Puerto Rican psychiatry patients: a preliminary report and potential implications for breast cancer patients. | BACKGROUND: The /"CYP2D6"/ liver enzyme, which metabolizes 25-30% of common medications, is highly polymorphic. Existing studies of Hispanics have focused on Mexicans and Mexican-Americans. The goal of the study was to identify the /"CYP2D6"/ alleles associated with reduced or negligible activities present in the Puerto Rican population. METHODS: The study cohort comprised 40 Puerto Rican /"psychiatric"/ patients referred because of suspected intolerance of drugs metabolized by /"CYP2D6"/, and five subjects without suspected adverse responses to these drugs. All subjects had both parents and all grandparents born in Puerto Rico. Genomic DNA was queried for 27 /"CYP2D6"/ alleles using the Roche AmpliChip P450 test. RESULTS: A total of 12 alleles were identified. The most common alleles were /"CYP2D6"/*1 > *2 > *4 > *41. The inactive alleles were *4 > * 5 > * 31 >*40; reduced activity alleles were *10 >* 17 > *9* = *29; active alleles were *1 > *2 > *35. Two subjects carried the rare *31 allele. Only one subject carried two non-functional alleles (/"CYP2D6"/*5/*40), and was predicted to be a poor metabolizer. CONCLUSIONS: Any conclusions should be interpreted with caution given the small population sample investigated. Nonetheless, our findings strongly suggest that Puerto Ricans exhibit distinct /"CYP2D6"/ allele frequencies and harbor a non-functional allele that is rare or absent in other populations and are highly valuable for the emerging practice of Personalized Medicine in admixed populations like Puerto Ricans. | [
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20810130 | Epistasis between HLA-DRB1 parental alleles in a Spanish cohort with multiple sclerosis. | BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) has been consistently associated with the HLA-DR2 haplotype and particularly with the HLA-DRB1*15 allele. Epistatic interactions between both parental alleles in the DRB1 loci have been shown to modify the MS susceptibility risk. This study investigated the frequencies of various HLA-DRB1 genotypes, their impact on MS susceptibility and their correlation with the clinical severity in a Spanish population. METHODS: A genotype was considered as the combination of the two parental DRB1 alleles. We compared the frequencies of the genotypes in a sporadic MS population (n=380) with those of an unrelated healthy control cohort (n=1088). We correlated the different genotypes with the age at onset, gender distribution, symptoms at onset, course of the disease and progression severity by means of the time to reach the progressive phase and EDSS scores of 3 and 6. RESULTS: We found 81 different genotypes. There were four different MS-predisposing genotypes. Three of them contained the DRB1*15 allele (DRB1*03/15, DRB1*04/15, and DRB1*08/15) and the fourth was homozygote for the DRB1*03 allele. The highest odds ratio was found with the genotype DRB1*08/15 (OR=3.88, 95% CI=1.83-8.26, p<0.01), followed by DRB1*03/03 (OR=3.15, 95% CI=1.93-5.14, p<0.01), DRB1*03/15 (OR=2.72, 95% CI=1.88-3.94, p<0.01) and DRB1*04/15 (OR=2.54, 95% CI=1.64-3.98, p<0.01). The DRB1*01/04 and the DRB1*15/15 genotypes were associated with a shorter time to reach an EDSS score of 6. CONCLUSIONS: Our results show the importance of epistatic interactions among the HLA-DRB1 alleles, modifying the risk for MS as well as its clinical severity. | Epistasis between /"HLA-DRB1"/ parental alleles in a Spanish cohort with /"multiple sclerosis"/. | BACKGROUND AND OBJECTIVE: /"Multiple sclerosis"/ (/"MS"/) has been consistently associated with the HLA-DR2 haplotype and particularly with the /"HLA-DRB1"/*15 allele. Epistatic interactions between both parental alleles in the /"DRB1"/ loci have been shown to modify the /"MS"/ susceptibility risk. This study investigated the frequencies of various /"HLA-DRB1"/ genotypes, their impact on /"MS"/ susceptibility and their correlation with the clinical severity in a Spanish population. METHODS: A genotype was considered as the combination of the two parental /"DRB1"/ alleles. We compared the frequencies of the genotypes in a sporadic /"MS"/ population (n=380) with those of an unrelated healthy control cohort (n=1088). We correlated the different genotypes with the age at onset, gender distribution, symptoms at onset, course of the disease and progression severity by means of the time to reach the progressive phase and EDSS scores of 3 and 6. RESULTS: We found 81 different genotypes. There were four different /"MS"/-predisposing genotypes. Three of them contained the /"DRB1"/*15 allele (/"DRB1"/*03/15, /"DRB1"/*04/15, and /"DRB1"/*08/15) and the fourth was homozygote for the /"DRB1"/*03 allele. The highest odds ratio was found with the genotype /"DRB1"/*08/15 (OR=3.88, 95% CI=1.83-8.26, p<0.01), followed by /"DRB1"/*03/03 (OR=3.15, 95% CI=1.93-5.14, p<0.01), /"DRB1"/*03/15 (OR=2.72, 95% CI=1.88-3.94, p<0.01) and /"DRB1"/*04/15 (OR=2.54, 95% CI=1.64-3.98, p<0.01). The /"DRB1"/*01/04 and the /"DRB1"/*15/15 genotypes were associated with a shorter time to reach an EDSS score of 6. CONCLUSIONS: Our results show the importance of epistatic interactions among the /"HLA-DRB1"/ alleles, modifying the risk for /"MS"/ as well as its clinical severity. | [
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"text_name": "HLA-DRB1"
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20810156 | ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. | BACKGROUND: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies. OBJECTIVE: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. CONCLUSION: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma. | ALOX5AP and /"LTA4H"/ polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. | BACKGROUND: Understanding the effects of interactions between multiple genes and /"asthma"/ medications may aid in the understanding of the heterogeneous response to /"asthma"/ therapies. OBJECTIVE: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and /"leukotriene A(4) hydrolase"/ (/"LTA4H"/) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with /"asthma"/, ALOX5AP and /"LTA4H"/ genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at /"LTA4H"/ single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at /"LTA4H"/ SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. CONCLUSION: /"LTA4H"/ and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with /"asthma"/. | [
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20810156 | ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. | BACKGROUND: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies. OBJECTIVE: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. CONCLUSION: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma. | /"ALOX5AP"/ and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. | BACKGROUND: Understanding the effects of interactions between multiple genes and /"asthma"/ medications may aid in the understanding of the heterogeneous response to /"asthma"/ therapies. OBJECTIVE: To identify modulating effects of /"arachidonate 5-lipoxygenase-activating protein"/ (/"ALOX5AP"/) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with /"asthma"/, /"ALOX5AP"/ and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at /"ALOX5AP"/ SNP rs10507391 or the minor allele at /"ALOX5AP"/ SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. CONCLUSION: LTA4H and /"ALOX5AP"/ gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with /"asthma"/. | [
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20812194 | The L55M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis. | Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that exhibits antioxidant and antiatherogenic activities. We examined a possible association between T172A (L55M) and T(-107)C polymorphisms and rheumatoid arthritis. These polymorphisms were determined in 88 rheumatoid arthritis patients and 78 healthy subjects, using the tetra-amplification refractory mutation system-PCR method. The prevalence of the PON1 55MM genotype was significantly greater among rheumatoid arthritis patients (17%) when compared to control subjects (5.2%) (odds ratio (OR) = 3.75; 95% confidence interval (CI) = 1.87-11.8, P = 0.025). In addition, the M allele was more frequent in rheumatoid arthritis patients (40%) than in healthy subjects (24.7%) (OR = 1.997; 95%CI = 1.243-3.210, P = 0.005). There were no significant differences in the -107C/T polymorphism in the promoter sequence of PON1 between rheumatoid arthritis and normal subjects (chi(2) = 0.861, P = 0.650). In conclusion, the PON1 55MM genotype is a risk factor for rheumatoid arthritis. | The L55M polymorphism of /"paraoxonase-1"/ is a risk factor for /"rheumatoid arthritis"/. | /"Paraoxonase-1"/ (/"PON1"/) is a high-density lipoprotein-associated enzyme that exhibits antioxidant and antiatherogenic activities. We examined a possible association between T172A (L55M) and T(-107)C polymorphisms and /"rheumatoid arthritis"/. These polymorphisms were determined in 88 /"rheumatoid arthritis"/ patients and 78 healthy subjects, using the tetra-amplification refractory mutation system-PCR method. The prevalence of the /"PON1"/ 55MM genotype was significantly greater among /"rheumatoid arthritis"/ patients (17%) when compared to control subjects (5.2%) (odds ratio (OR) = 3.75; 95% confidence interval (CI) = 1.87-11.8, P = 0.025). In addition, the M allele was more frequent in /"rheumatoid arthritis"/ patients (40%) than in healthy subjects (24.7%) (OR = 1.997; 95%CI = 1.243-3.210, P = 0.005). There were no significant differences in the -107C/T polymorphism in the promoter sequence of /"PON1"/ between /"rheumatoid arthritis"/ and normal subjects (chi(2) = 0.861, P = 0.650). In conclusion, the /"PON1"/ 55MM genotype is a risk factor for /"rheumatoid arthritis"/. | [
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20816194 | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from /"atopic dermatitis"/. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous /"signal transducer and activator of transcription 3"/ (/"STAT3"/) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and /"atopic dermatitis"/. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), /"STAT3"/ genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous /"STAT3"/ missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with /"STAT3"/ mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type /"STAT3"/ and control subjects. Only 1 patient with wild-type /"STAT3"/ had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type /"STAT3"/ and 33 patients with /"STAT3"/ mutations. Internal abscesses and severe infections were exclusively seen in patients with /"STAT3"/ mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type /"STAT3"/. CONCLUSION: We expanded the number of /"STAT3"/ mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with /"STAT3"/ mutations, supporting early diagnosis of AD-HIES. | [
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20816194 | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. | Diagnostic approach to the /"hyper-IgE syndromes"/: immunologic and clinical key findings to differentiate /"hyper-IgE syndromes"/ from atopic dermatitis. | BACKGROUND: /"Hyper-IgE syndromes"/ (/"HIES"/) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous /"signal transducer and activator of transcription 3"/ (/"STAT3"/) mutations with autosomal dominant (AD)-/"HIES"/ allows the differentiation of AD-/"HIES"/ from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-/"HIES"/ to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), /"STAT3"/ genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having /"HIES"/. RESULTS: Heterozygous /"STAT3"/ missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with /"STAT3"/ mutations with /"HIES"/ showed significantly lower T(H)17 cell counts compared with patients with wild-type /"STAT3"/ and control subjects. Only 1 patient with wild-type /"STAT3"/ had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type /"STAT3"/ and 33 patients with /"STAT3"/ mutations. Internal abscesses and severe infections were exclusively seen in patients with /"STAT3"/ mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type /"STAT3"/. CONCLUSION: We expanded the number of /"STAT3"/ mutations and validated that the NIH score sensitively identifies patients with /"HIES"/. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-/"HIES"/ with /"STAT3"/ mutations, supporting early diagnosis of AD-/"HIES"/. | [
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20816194 | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. | Diagnostic approach to the /"hyper-IgE syndromes"/: immunologic and clinical key findings to differentiate /"hyper-IgE syndromes"/ from atopic dermatitis. | BACKGROUND: /"Hyper-IgE syndromes"/ (/"HIES"/) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum /"IgE"/ levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-/"HIES"/ allows the differentiation of AD-/"HIES"/ from disorders associated with eczema and increased serum /"IgE"/ levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-/"HIES"/ to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having /"HIES"/. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with /"HIES"/ showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with /"HIES"/. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-/"HIES"/ with STAT3 mutations, supporting early diagnosis of AD-/"HIES"/. | [
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20816194 | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. | Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. | BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum /"IgE"/ levels, and /"eczema"/. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with /"eczema"/ and increased serum /"IgE"/ levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. | [
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} | No |
20842733 | Variants in folate pathway genes as modulators of genetic instability and lung cancer risk. | Genetic instability plays a crucial role in cancer development. The genetic stability of the cell as well as DNA methylation status could be modulated by folate levels. Several studies suggested associations between polymorphisms in folate genes and alterations in protein expression and variations in serum levels of the folate. The objective of this study was to investigate the effect of folate pathway polymorphisms on modulating genetic instability and lung cancer risk. Genotyping of 5 SNPs in folate pathway genes and cytokinesis-blocked micronucleus cytome assay analysis (to determine the genetic instability at baseline and following NNK treatment) was conducted on 180 lung cancer cases and 180 age-, gender-, and smoking-matched controls. Our results showed that individually, folate pathway SNPs were not associated with cytogenetic damage or lung cancer risk. However, in a polygenic disease such as lung cancer, gene-gene interactions are expected to play an important role in determining the phenotypic variability of the diseases. We observed that interactions between MTHFR677, MTHFR1298, and SHMT polymorphisms may have a significant impact on genetic instability in lung cancer patients. With regard to cytogenetic alterations, our results showed that lymphocytes from lung cancer patients exposed to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK] had considerably increased frequency of cytogenetic damage in presence of MTHFR 677, MTHFR 1298, and SHMT allelic variants. These findings support the notion that significant interactions may potentially modulate the lung cancer susceptibility and alter the overall the repair abilities of lung cancer patients when exposed to tobacco carcinogens such as NNK. | Variants in folate pathway genes as modulators of genetic instability and /"lung cancer"/ risk. | Genetic instability plays a crucial role in cancer development. The genetic stability of the cell as well as DNA methylation status could be modulated by folate levels. Several studies suggested associations between polymorphisms in folate genes and alterations in protein expression and variations in serum levels of the folate. The objective of this study was to investigate the effect of folate pathway polymorphisms on modulating genetic instability and /"lung cancer"/ risk. Genotyping of 5 SNPs in folate pathway genes and cytokinesis-blocked micronucleus cytome assay analysis (to determine the genetic instability at baseline and following NNK treatment) was conducted on 180 /"lung cancer"/ cases and 180 age-, gender-, and smoking-matched controls. Our results showed that individually, folate pathway SNPs were not associated with cytogenetic damage or /"lung cancer"/ risk. However, in a polygenic disease such as /"lung cancer"/, gene-gene interactions are expected to play an important role in determining the phenotypic variability of the diseases. We observed that interactions between MTHFR677, /"MTHFR"/1298, and SHMT polymorphisms may have a significant impact on genetic instability in /"lung cancer"/ patients. With regard to cytogenetic alterations, our results showed that lymphocytes from /"lung cancer"/ patients exposed to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK] had considerably increased frequency of cytogenetic damage in presence of /"MTHFR"/ 677, /"MTHFR"/ 1298, and SHMT allelic variants. These findings support the notion that significant interactions may potentially modulate the /"lung cancer"/ susceptibility and alter the overall the repair abilities of /"lung cancer"/ patients when exposed to tobacco carcinogens such as NNK. | [
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