KCNJ11 rs5219 Gene Polymorphism Is Associated With T2DM in a Population of Bangladesh: A Case-Control Study

KCNJ11 rs5219基因多态性与孟加拉国人群中的2型糖尿病相关:一项病例对照研究

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Abstract

Introduction: As a polygenic disorder, Type 2 diabetes mellitus is a prevalent disease developed by many multigenetic factors, of which multiple genes located on different chromosomes contribute to its susceptibility. The KCNJ11 gene is involved in the Kir6.2 proteins that help release insulin from the potassium channels in pancreatic beta cells. Many studies have found that KCNJ11 polymorphism is significantly associated with the incidence of T2DM. Therefore, this study was carried out to investigate the association between KCNJ11 gene polymorphism and T2DM in the Bangladeshi population. Materials and Methods: In a case-control study (n = 697), 326 nondiabetic controls and 371 diabetic subjects (diagnosed based on American Diabetes Association criteria) were recruited for this study. The serum fasting glucose, lipid profiles, creatinine, alanine aminotransferase (ALT), HbA(1C), and serum insulin level were measured by standard methods. HOMA-B%, HOMA-S%, and HOMA-IR were calculated using HOMA-SIGMA software Version 2.2. A standard formula calculated QUICKI and Secretory-HOMA. The chemical method was used for DNA extraction from whole blood samples. The PCR-RFLP method was used to detect KCNJ11 polymorphisms by restriction enzyme (BanII) digestion. As appropriate, data were analyzed using an independent t-test, chi-square, or Fisher exact test. p < 0.05 was considered significant. Results: The frequency of the risk allele K was significantly higher in the T2DM group than control (p ≤ 0.01). The frequency of the KK genotype was higher among the T2DM group (3.77% vs. 1.84%, p < 0.05), and the frequency of the EK genotype was significantly higher among the T2DM than the control group (42.86% vs. 27.91%, p < 0.001). The EE genotype was significantly associated with T2DM in the dominant model EE + EK with an OR of 2.06 (95% CI 1.51-2.82, p ≤ 0.001). Conclusion: This study showed that rs5219 polymorphism of the KCNJ11 gene is a significant risk factor for Type 2 diabetes mellitus in the Bangladeshi population.

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