The Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India

Abstract

Background:Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 (rs7566605) gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects.Methods:The variants were investigated for association in 642 obese and non-obese individuals. The genotyping of INSIG2 (rs7566605) single nucleotide polymorphism was analyzed by the TaqMan allelic discrimination protocol.Results:A significant association was observed for INSIG2 (rs7566605) single nucleotide polymorphism with obesity and obesity-related phenotypes. Furthermore, a significant relationship was found between the rs7566605 and insulin, homeostasis model of assessment-insulin resistance, the percentage of body fat, fat mass, leptin, and adiponectin.Conclusion:The present study observed significant association between INSIG2 (rs7566605) single nucleotide polymorphism and obesity, as well as obesity-associated phenotypes in North Indian population.

Altered macronutrient composition and genetics influence the complex transcriptional network associated with adiposity in the Collaborative Cross

“…Similar to Insig1 , Insig2 obstructs processing of SREBPs by binding to SREBP cleavage-activating protein in the ER, which results in blockage of cholesterol synthesis [ 100 ]. Genetic variants in INSIG2 (rs75666605) have been associated with severe obesity in a North Indian human population [ 68 ] and increased blood pressure and triglyceride levels in Brazilian obese patients [ 60 ]. Differentially expressed by both strain and diet, IRS2 is a vital mediator of insulin signaling since it acts as an immediate downstream substrate of insulin receptors and activates a cascade of serine-protein kinases to modulate numerous metabolic processes [ 2 , 14 ].…”

ESI Clinical Practice Guidelines for the Evaluation and Management of Obesity In India

“…[ 133 134 ] Polymorphisms of INSIG2 gene have been associated with obesity in North Indian subjects. [ 135 ] Polymorphisms of FTO and vitamin D receptor genes may influence the response to weight-loss intervention in Indian patients. [ 136 ] However, since many genes and their variants contribute synergistically to the development of obesity, polygenic risk scores are probably superior in predicting obesity risk than individual variants.…”

Impact of Genetic Variations and Epigenetic Mechanisms on the Risk of Obesity

“…Currently, two gene variants, i.e., of MC4R, already known as the most common cause of monogenic obesity, and FTO-associated gene, have been identified, with small but replicable effects on body weight. Further studies are fundamental to confirm the involvement in the regulation of body weight of a third gene, i.e., insulin-induced gene 2 (INSIG2) [46,[63][64][65][66].…”