Genetic Association of FTO gene variants (rs17817449 T>G and rs9939609 T>A) with obesity and its related Phenotypes in North Indian Punjabi Population

Abstract

Fat mass and obesity associated (FTO) gene belongs to the non-heme Fe (II) and 2 oxoglutarate dependent dioxygenase superfamily. FTO gene has been evolved as a potent genetic risk factor for the development of obesity. To establish the potential association between FTO rs17817449 T > G and rs9939609 T > A polymorphisms and obesity risk in north Indian Punjabi population, a total of 333 obese and 338 non-obese control subjects were randomly selected. Both the FTO gene polymorphisms rs17817449 (TT vs GG: odds ratio (OR), 2.30; 95% confidence interval (CI), 1.39–3.79) and rs9939609 (TT vs AA: odds ratio (OR), 2.78; 95% confidence interval (CI), 1.37–5.64) were significantly associated with obesity and conferred 2-fold and 3-fold risk toward the development of obesity respectively. Logistic regression analysis determined the significant association under the recessive genetic model (OR = 2.29; 95%CI: 1.47–3.57) and (OR = 5.25; 95%CI: 2.68–10.28) respectively for rs17817449 and rs9939609 thereby confirming the major role of environmental and anthropometric factors in this population. Haplotype analysis revealed that TA haplotype conferred 4-fold risk towards obesity (p = 0.0001). The rs17817449G allele and the obesity associated covariates accounted for 55%, 49%, 42%, 34%, 31% and 22% variability in body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and triglyceride (TG) respectively. For rs9939609A allele contributed 98%, 82%, 54%, 59%, 71% and 84% variability in BMI, WC, WHtR, SBP, DBP, TG respectively in obese individuals. Therefore, the present study suggested that both the polymorphisms of FTO gene (rs17817449 T > G and rs9939609 T > A) are relevant markers of obesity in the north Indian Punjabi population and both plays an important role in an individual’s predisposition towards obesity.