单位：[1]Department of Endocrinology, Key Laboratory of Diabetes Prevention and Control of China-Japan Friendship Hospital, Beijing, China,[2]Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America,[3]Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, China,[4]Department of Endocrinology, Henan Province People’s Hospital, Zhengzhou, Henan, China,[5]Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China,[6]Department of Endocrinology, Xinjiang Uygur Autonomous Region’s Hospital, Urmqi, Xinjiang, China,[7]Department of Endocrinology, Fujian Provincial Hospital, Fuzhou, Fujian, China,[8]Department of Endocrinology, Peking University First Hospital, Beijing, China,[9]Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing, China,[10]Department of Endocrinology, Sun Yat-sen University Third Hospital, Guangzhou, Guangdong, China,中山大学附属第三医院[11]Department of Endocrinology, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China,[12]Department of Endocrinology, Peking University People’s Hospital, Beijing, China,[13]Department of Endocrinology, First Affiliated Hospital, Chinese Medical University, Shenyang, Liaoning, China,[14]Department of Endocrinology, Shanxi Province People’s Hospital, Taiyuan, Shanxi, China,[15]Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, Sichuan, China,四川大学华西医院[16]Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China,[17]Department of Endocrinology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China,[18]Department of Endocrinology, Xiangya Second Hospital, Changsha, Hunan, China,[19]Department of Epidemiology, Peking Union Medical College, Beijing, China
Background and Aims: Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population. Methods: We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing beta-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively. Results: Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75x10(-4); OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54x10(-3)). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81x10(-2)) and that of GNPDA2 was attenuated (P = 1.26x10(-1)), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04x10(-2)). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05). Conclusions: This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population.
基金：
Chinese Medical Association Foundation; Sanofi (China) Investment Company Limited; National 973 ProgramNational Basic Research Program of China [2011CB504001]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2012M520200]; Fogarty International Center of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Fogarty International Center (FIC) [D43TW009107]; Eunice Kennedy Shriver National Institute of Child Health & Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [K12HD043451]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENTUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [K12HD043451] Funding Source: NIH RePORTER; FOGARTY INTERNATIONAL CENTERUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Fogarty International Center (FIC) [D43TW009107] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Endocrinology, Key Laboratory of Diabetes Prevention and Control of China-Japan Friendship Hospital, Beijing, China,
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推荐引用方式(GB/T 7714)：
Xiaomu Kong,Xuelian Zhang,Qi Zhao,et al.Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population[J].PLOS ONE.2014,9(8):doi:10.1371/journal.pone.0104486.
APA：
Xiaomu Kong,Xuelian Zhang,Qi Zhao,Jiang He,Li Chen...&Wenying Yang.(2014).Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population.PLOS ONE,9,(8)
MLA：
Xiaomu Kong,et al."Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population".PLOS ONE 9..8(2014)
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