Physical activity attenuates the association between the IRS1 genotype and childhood obesity in Chinese children

Abstract Background s and Aims: The insulin receptor substrate 1 ( IRS1 ) rs2943650 was found to be associated with obesity in adults, but the association has not been evaluated in children. The present study aimed to examine whether IRS1 rs2943650 was associated with obesity in Chinese children, and explore the interaction between rs2943650 and physical activity. Methods and results IRS1 rs2943650 was genotyped in 3303 Chinese children aged 6-18 years from four independent studies. Logistic regression and linear regression were performed to examine associations. Meta-analyses were conducted to pool the results of four independent studies. The C-allele carriers of rs2943650 showed a 29% higher risk of obesity than non-carriers (OR (95% CI) =1.29 (1.05, 1.58), P =0.02), and a 0.41 kg/m 2 increase in BMI (β (95% CI) =0.41 (0.05, 0.78) kg/m 2 , P =0.02). We also observed significant interactions between rs2943650 and physical activity/sedentary behaviors on obesity ( P for interaction P =0.005). Conclusions We found that IRS1 rs2943650 was significantly associated with BMI and the risk of childhood obesity. And we also found significant interaction between IRS1 rs2943650 polymorphism and physical activity/sedentary behaviors on childhood obesity. Our study would provide novel insights into the function of the IRS1 gene, and the implementation of effective intervention strategies of childhood obesity.