Interaction analysis of gene variants of TCF7L2 and body mass index and waist circumference on type 2 diabetes

Abstract

Type 2 diabetes (T2D) is a complex metabolic disease with numerous risk factors, including a growing number of genetic susceptibility variants. The TCF7L2 gene is closely associated with an increased risk of type 2 diabetes, but the association of TCF7L2 with weight-related traits in humans is unclear. The purpose of this study was to determine if TCF7L2 variants and body mass index/waist circumference (BMI/WC) act synergistically to influence the incidence of type 2 diabetes in a Chinese population. This is a large sample, case-control study. We recruited 1842 Chinese type 2 diabetes patients and 7777 healthy controls and collected demographic and anthropometric characteristics and blood samples. We extracted DNA and genotyped the TCF7L2 single nucleotide polymorphisms rs7903146 and rs290487 in all participants. There were significant linear interactions between rs7903146 and BMI/WC and elevated blood glucose (P<0.001); rs290487 and BMI/WC also showed a linear interaction with blood glucose levels (P<0.001). The interaction was stronger at higher BMI (>21.02) and higher WC (>66.77cm). The additive interaction of rs 290487 and overweight/obesity variables yielded a significant increase in the risk for T2D. RERI (relative excess risk of interaction) was 2.949 (95%CI: 1.700-4.198), AP (attributable proportion due to interaction) was 0.391 (95%CI: 2.281-0.502), and SI (synergy index) was 1.822 (95%CI: 1.463-2.268). Additionally, there was a significant interaction between rs 290487 and abdominal obesity on the risk of T2D (RERI: 2.642, 95%CI: 1.384-3.900; AP: 0.350, 95%CI: 0.231-0.468; SI: 1.675, 95%CI: 1.348-2.083). These results show that a TCF7L2 gene-BMI interaction or gene-WC interaction may play an important role in the risk for T2D in the Chinese population.