Liangchang Xiu1, Meihua Lin1, Weiwei Liu1, Danli Kong1, Zhenghui Liu1, Yang Zhang1, Ping Ouyang1, Yan Liang2, Shouqiang Zhong2, Can Chen3, Xin Jin4, Xuejin Fan5, Jiheng Qin1, Xiaolei Zhao1, Shaoqi Rao1, Yuanlin Ding1. 1. 1 Department of Epidemiology and Medical Statistics, School of Public Health, and Institute of Medical Systems Biology, Guangdong Medical College , Dongguan, Guangdong, China . 2. 2 Department of Endocrinology and Metabolism, Maoming People's Hospital , Maoming, Guangdong, China . 3. 3 Department of Internal Cardiology, the Affiliated Hospital of Guangdong Medical College , Zhanjiang, Guangdong, China . 4. 4 Guanlan People's Hospital , Baoan District, Shenzhen, Guangdong, China . 5. 5 Shilong Boai Hospital , Dongguan, Guangdong, China .
Abstract
AIM: The aim of this study was to assess the associations of six single nucleotide polymorphisms (SNPs) of three genes (DRD3, COMT, and SCL6A4) with type 2 diabetes mellitus (T2DM) in Southern Chinese. SUBJECTS AND METHODS: Five hundred ninety-five cases with T2DM and 725 healthy controls of Han origin were recruited from six hospitals in Guangdong Province, Southern China. Fasting serum concentrations of markers of interest (total cholesterol, triglyceride, plasma glucose, etc.) were measured in hospitals. SNP genotyping was performed using a custom-by-design 2-×48-Plex SNPscan™ kit (Genesky Biotechnologies Inc., Shanghai, China). Single-point SNP analysis, haplotype analysis, and SNP-SNP interactions were carried out. RESULTS: SNP rs4646312 in COMT achieved statistical significance in both allelic association and genotypic association and even after adjusting covariates (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.04-1.53; P=0.021). Two haplotypes consisting of rs4646312 and rs4680 were also significantly associated with T2DM, of which C-G was a protective haplotype for T2DM (OR=0.83; 95% CI, 0.70-0.98; P=0.029), whereas T-A was a risk one (OR=1.23, 95% CI, 1.03-1.46; P=0.022). Interaction analysis identified a significant epistatic effect between rs4680 in COMT and rs2066713 in SCL6A4 after adjusting for covariates (OR=3.59, 95% CI, 1.72-7.48; P=0.001 for dominant-dominant model). However, only the interaction between rs4680 and rs2066713 was significant, and haplotype T-A showed a marginally increased risk after Bonferroni correction. CONCLUSIONS: The genetic polymorphisms in COMT and SCL6A4 confer significant effects in joint actions to T2DM in Southern Chinese.
AIM: The aim of this study was to assess the associations of six single nucleotide polymorphisms (SNPs) of three genes (DRD3, COMT, and SCL6A4) with type 2 diabetes mellitus (T2DM) in Southern Chinese. SUBJECTS AND METHODS: Five hundred ninety-five cases with T2DM and 725 healthy controls of Han origin were recruited from six hospitals in Guangdong Province, Southern China. Fasting serum concentrations of markers of interest (total cholesterol, triglyceride, plasma glucose, etc.) were measured in hospitals. SNP genotyping was performed using a custom-by-design 2-×48-Plex SNPscan™ kit (Genesky Biotechnologies Inc., Shanghai, China). Single-point SNP analysis, haplotype analysis, and SNP-SNP interactions were carried out. RESULTS: SNP rs4646312 in COMT achieved statistical significance in both allelic association and genotypic association and even after adjusting covariates (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.04-1.53; P=0.021). Two haplotypes consisting of rs4646312 and rs4680 were also significantly associated with T2DM, of which C-G was a protective haplotype for T2DM (OR=0.83; 95% CI, 0.70-0.98; P=0.029), whereas T-A was a risk one (OR=1.23, 95% CI, 1.03-1.46; P=0.022). Interaction analysis identified a significant epistatic effect between rs4680 in COMT and rs2066713 in SCL6A4 after adjusting for covariates (OR=3.59, 95% CI, 1.72-7.48; P=0.001 for dominant-dominant model). However, only the interaction between rs4680 and rs2066713 was significant, and haplotype T-A showed a marginally increased risk after Bonferroni correction. CONCLUSIONS: The genetic polymorphisms in COMT and SCL6A4 confer significant effects in joint actions to T2DM in Southern Chinese.
Authors: M A Daniels; C Kan; D M Willmes; K Ismail; F Pistrosch; D Hopkins; G Mingrone; S R Bornstein; A L Birkenfeld Journal: Pharmacogenomics J Date: 2016-07-19 Impact factor: 3.550
Authors: Kenneth J Mukamal; Kathryn T Hall; Kathleen A Jablonski; Ling Chen; Maegan Harden; Benjamin R Tolkin; Ted J Kaptchuk; George A Bray; Paul M Ridker; Jose C Florez; Daniel I Chasman Journal: Metabolism Date: 2016-04-14 Impact factor: 8.694