Association of genetic variants in TOMM7 gene and gene environment interaction with type 2 diabetes in Chinese Dong population

Abstract

To investigate the association of 7 novel genetic loci identified in a recent genome-wide association studies (GWAS) with T2DM in Chinese Dong populations. A case-controlled study was performed in individuals of Chinese Dong nationality. The genotypes of PARD3B (rs849230), LOC729993 (rs149228), EPHA4 (rs16862811), HNT (rs3099797), PTPRD (rs17584499 and rs649891), TOMM7 (rs2240727) genes were determined by Multiplex PCR-SNaPshot. The independent association between each polymorphism and T2DM was assessed by unconditional binary logistic regression analysis. The gene-environment interaction was assessed by marginal structural linear odds model. A total of 209 cases of T2DM and 209 control subjects were enrolled in the study. The polymorphism of rs2240727 in TOMM7 gene was associated with T2DM (OR=1.50, per copy of the risk T allele, P=0.004). In addition, CT (OR=2.07, 95% CI: 1.14-3.76) and TT (OR=2.75, 95% CI: 1.46-5.17) were risk genotypes for T2DM. After the correction for multiple test, the association remained significant (all P<0.05). After adjustment for the confounders of age, gender, and BMI, the association remained significant (P<0.05). The results of interaction analysis indicated that there were interaction between rs2240727 locus and BMI, WHR, hypertension and family history of diabetes. After adjustment for age and gender, the results of relative excess risk of interaction (RERI) were 1.5430 (95% CI: 0.5797-2.5062), 2.6520 (95% CI: 1.7516-3.5524), 2.9131 (95% CI: 1.7959-4.0303), 4.2062 (95% CI: 1.1686-8.2439), respectively (all P<0.05). The rs2240727 genetic variant in TOMM7 is associated with T2DM in Chinese Dong population. There is positive interaction between rs2240727 and BMI, WHR, hypertension as well as family history of diabetes.