Abstract

Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene may be key agents in the etiology of type 2 diabetes mellitus (T2DM). In the present case-control study, we aimed to assess the possible relationship of TCF7L2 polymorphisms with T2DM and determine the effect of TCF7L2 polymorphisms on the level of fasting plasma glucose (FPG) in Eastern Chinese Han subjects. The TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms were genotyped by SNPscan genotyping assays in 502 subjects with T2DM and 782 non-diabetic controls. After adjusting for age, gender, drinking, smoking and body mass index (BMI), the association of TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms with T2DM was determined. We found that TCF7L2 rs290481 T>C polymorphism increased the susceptibility of T2DM in the overall comparison. In subgroup analyses by age, sex, BMI, alcohol use and smoking status, a significantly increased risk of T2DM was also found in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. The relationship of TCF7L2 rs290481 T>C polymorphism with the biochemistry characteristics in controls was also assessed. We found that TCF7L2 rs290481 T>C polymorphism significantly increased the level of FPG in controls. Our findings suggest that TCF7L2 rs290481 T>C polymorphism is associated with T2DM in Eastern Chinese Han population and links to variations in FPG level. In addition, these relationships are more pronounced in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. A comprehensive fine-mapping study with functional investigation is needed to confirm or refute these potential correlations.

Highlights

  • Type 2 diabetes mellitus (T2DM), a chronic metabolic disease, is a common form of diabetes

  • Our findings suggest that transcription factor 7-like 2 (TCF7L2) rs290481 T>C polymorphism is associated with type 2 diabetes mellitus (T2DM) in Eastern Chinese Han population and links to variations in fasting plasma glucose (FPG) level

  • We found that TCF7L2 rs290481 T>C polymorphism significantly increased the level of fasting plasma glucose (FPG) and high-density lipoprotein cholesterol (HDL-C) in controls

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Summary

Introduction

Type 2 diabetes mellitus (T2DM), a chronic metabolic disease, is a common form of diabetes. T2DM is primarily characterized by disturbance of energy metabolism, relative insulin deficiency and/or insulin resistance. T2DM is a complex metabolic disorder resulting from multiple genetic components and environmental risk factors. The lipid metabolism and insulin signal transduction candidate genes may participate in the pathogenesis of T2DM. The variants of these candidate genes could change the expression of protein and lead to abnormal signal transduction or metabolic disorder. These variants may influence the susceptibility of T2DM

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