Investigation of Type 2 Diabetes Risk Alleles Support CDKN2A/B, CDKAL1, and TCF7L2 As Susceptibility Genes in a Han Chinese Cohort

Background Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings Selected type 2 diabetes–associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B , CDKAL1 , TCF7L2 , TCF2 , MC4R , and PPARG showed a nominal association with type 2 diabetes ( P ≤0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12–1.43) P  = 1.8*10 −4 ; CDKAL1 rs10946398, OR: 1.23 (1.09–1.39); P  = 7.1*10 −4 , and TCF7L2 rs7903146, OR: 1.61 (1.19–2.18) P  = 2.3 * 10 −3 . Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose ( P  = 0.002), postprandial plasma glucose ( P  = 0.002), and fasting C-peptide levels ( P  = 0.006) in the diabetic patients, and with BMI in controls ( P  = 0.033). Conclusions/Significance We have identified significant association between variants in CDKN2A/B , CDKAL1 and TCF7L2 , and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities.