Objectives: To evaluate the relationship between transcription factor 7-like 2 (TCF7L2) gene polymorphism and diabetic nephropathy (DN) risk, as well as the effect of gene-environment interactions on DN risk in Chinese Han population.
Methods: The Hardy-Weinberg equilibrium (HWE) and the relationship between TCF7L2 gene single nucleotide polymorphism (SNPs) and DN susceptibility were evaluated by SNPStats. The interaction among four SNPs and environmental factors were tested by generalized multifactor dimensionality reduction (GMDR). The consistency of cross validation, accuracy of test balance and sign test were calculated to evaluate the interaction of each selection. The logistic regression was used to test the interaction between rs7903146 and current smoking by stratified analysis.
Results: Logistic regression analysis indicated that the DN risk of rs7903146-T allele carriers were obviously higher than that in CC genotype carriers (CT + TT versus CC), adjusted OR (95 %CI) = 1.64 (1.24-2.06). However, we also discovered that people with rs12255372, rs11196205 and rs290487 minor allele had non-significant difference risk of DN compared with people with major allele. The GMDR model found a significant two-locus model (p = 0.0100) including rs7903146 and current smoking, suggesting a potential gene-environment interaction between rs7903146 and current smoking. Compared with never smokers with rs7903146- CC genotype, current smokers with rs7903146- CT or TT genotype had the highest DN risk. After covariate adjustment, OR (95 %CI) was 2.15 (1.58-2.78).
Conclusions: We found a significant relationship of rs7903146-T alleles, and the interaction between rs7903146-T and current smoking with increased DN risk.
Keywords: Diabetic nephropathy; Interaction; Polymorphisms; Transcription factor 7-like 2.