Association of Genetic Variants of KCNJ11 and KCNQ1 Genes with Risk of Type 2 Diabetes Mellitus (T2DM) in the Indian Population: A Case-Control Study.

Vasiuddin Khan,Arshad Husain Rahmani,Shahbaz Khan,Ahmad Almatroudi,Amit Kumar Verma,Yamini Goyal,Sowmya Ramachandran,M Y Shareef,Deepti Bhatt,Rameez Hasan,Babita Meena,Kapil Dev,Mohammed A Alsahli

doi:10.1155/2020/5924756

Abstract

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. The interaction between various genetic variants and environmental factors triggers T2DM. The aim of this study was to find risk associated with genetic variants rs5210 and rs2237895 of KCNJ11 and KCNQ1 genes, respectively, in the development of T2DM in the Indian population. A total number of 300 cases of T2DM and 100 control samples were studied to find the polymorphism in KCNJ11 and KCNQ1 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different compared to the control population. KCNJ11 rs5210 and KCNQ1 rs2237895 variants were found to be significantly associated with risk of T2DM in dominant (KCNJ11: OR, 2.07; 95% CI, 1.30–3.27; p − 0.001; KCNQ1: OR, 2.33; 95% CI, 1.46–3.70; p − 0.0003) and codominant models (KCNJ11: OR, 1.76; 95% CI, 1.09–2.84; p − 0.020; KCNQ1: OR, 1.85; 95% CI, 1.16–2.95; p − 0.009). We also compared clinicopathological characteristics between cases and control and observed a significant difference in all the parameters except HDL, gender, and family history. In this study, clinicopathological data with a carrier of a variant allele of both KCNJ11 and KCNQ1 genes were also analysed, and a significant association was found between the carrier of a variant allele with gender and PPG in KCNJ11 and with triglyceride in KCNQ1. We confirm the significant association of KCNJ11 (rs5210) and KCNQ1 (rs2237895) gene polymorphism with T2DM, indicating the role of these variants in developing risk for T2DM in Indian population.

Highlights

Type 2 Diabetes is a chronic metabolic disorder described by reduced insulin secretion and insulin action and hypergycemia
We found a significant relationship between KCNJ11 rs5210 A ⟶ G gene polymorphism and Type 2 diabetes mellitus (T2DM) risk under the dominant (OR, 2.07; 95% CI, 1.30–3.27; p − 0.001) and codominant models (OR, 1.76; 95% CI, 1.09–2.84; p − 0.020), whereas no significant relationship was found under the recessive model (OR, 1.54; 95% CI, 0.74–3.20; p − 0.239)
We found a significant relationship between KCNQ1 rs2237895 A⟶C gene polymorphism and T2DM risk under the dominant model (OR, 2.33; 95% CI, 1.46–3.70; p − 0.0003) and codominant model

Summary

Introduction

Type 2 Diabetes is a chronic metabolic disorder described by reduced insulin secretion and insulin action and hypergycemia. Among different types of diabetes, T2DM is the most common wherein multiple environmental and genetic factors are associated with the development of this disease [1, 2]. As per the International Diabetes Federation’s (IDF). India is home to 74 million people with diabetes mellitus, with approximately 8.7% prevalence among the adult population, and considered as the “diabetes capital” of the world (IDF, 8th edition). Genome-wide association studies (GWAS) found various susceptibility genes for diabetes [3,4,5]. The International Journal of Endocrinology mechanisms these genes follow for the development of diabetes are still not clear. Many gene polymorphism findings demonstrated the association of various SNPs in the pathogenesis of T2DM, and in different populations, each SNP may exhibit dissimilar association with T2DM. Many gene polymorphism findings demonstrated the association of various SNPs in the pathogenesis of T2DM, and in different populations, each SNP may exhibit dissimilar association with T2DM. erefore, there is a necessity to discover various genetic risk markers of T2DM for its prevention and treatment

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Conclusion