TCF7L2 gene variants predispose to the development of type 2 diabetes mellitus among individuals with metabolic syndrome.

Abstract

Transcription factor 7-like 2 (TCF7L2) gene variants rs12255372 and rs7903146 have been consistently shown to raise genetic risk for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the possible role of these variants in the development of impaired glucose metabolism (IGM), including impaired fasting glucose (IFG) or T2DM, in patients with metabolic syndrome (MS). The study population consisted of 228 patients with MS who were divided into two groups. The first group consisted of 148 patients with MS and IGM [39M/109F, 59.8 ± 14.6 (mean ± SD) years] and the second group of 80 patients with MS and normoglycemia (NGM) (16M/64F, 56.1 ± 15.8years). The diagnosis of MS was based on the criteria proposed by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Anthropometric parameters including BMI and waist circumference were recorded and blood samples were obtained after overnight fasting for biochemical tests. The rs12255372 and rs7903146 TCF7L2 polymorphisms were genotyped in peripheral blood leucocytes. Analysis of the distribution of the TCF7L2 polymorphic alleles revealed that the frequency of the T allele of the TCF7L2 variant rs12255372 was 38.2% in the study population, while the frequency of the T allele of the TCF7L2 rs7903146 variant was 35.3%. The T allele of the rs12255372 variant was more frequently present in patients with MS and IGM (48.3%) compared to patients with MS and NGM (19.4%, p < 0.001). Also, the T allele of rs7903146 was more frequently present in patients with MS and IGM (44.6%) compared to patients with MS and NGM (18.1%, p < 0.001). Logistic regression analysis followed and revealed that the presence of the T allele for both rs12255372 and rs7903146 TCF7L2 gene variants is a very powerful predictor of the presence of glucose disorders, increasing the risk more than fourfold in patients with MS and after adjustment for potential confounders, such as age, gender, BMI, and waist circumference (TCF7L2 rs12255372: Exp(B) 4.917, p < 0.001 and TCF7L2 rs7903146: Exp(B) 5.460, p < 0.001). The presence of the rs12255372 and rs7903146 TCF7L2 gene variants plays an important role in the development of T2DM among individuals with MS. These findings support the notion that among subjects with MS, those who finally develop T2DM have a genetic predisposition to β-cell dysfunction.