TCF7L2 gene variant rs7903146 affects the risk of Type 2 Diabetes by modulating incretin secretion

ABSTRACT

Background: Type2 diabetes mellitus (T2DM) is a highly inheritable disease. Transcription factor 7- like 2 (TCF7L2) gene regulates the expression of glucagon-like peptide 1 (GLP-1) in L cells of small intestine. GLP1 plays a critical role in blood glucose homeostasis by stimulating postprandial insulin secretion and increasing insulin sensitivity. Aim of the study TCF7L2 gene variants may affect the susceptibility to Type 2 diabetes by altering GLP-1 levels. Materials and methods: This case-control study was conducted with 90 newly diagnosed patients with Type2 diabetes mellitus as cases and 90 age and sex-matched healthy volunteers as controls. TCF7L2 rs7903146 genotyping was done and we also estimated Fasting and postprandial GLP -1 level, Fasting and Postprandial insulin level and calculated HOMA-IR in both cases and controls. Results: Out study showed that T+ genotype, lower fasting GLP-1 level and lower postprandial GLP1 levels were more observed among cases as compared to controls. Low mean GLP 1 activity, high Mean HOMA-IR, low postprandial insulin, low percentage rise in insulin were observed among T+ genotype than among T- genotypic individuals. Conclusion: Hence, the study concludes that T+ genotype causes a decrease in GLP-1 levels, which in turn by decreasing postprandial insulin levels and by increasing insulin resistance increases the risk of Type2 diabetes.