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

Background 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 investigate the interaction between rs2943650 and physical activity. Methods and results: IRS1 rs2943650 was genotyped in 3303 Chinese children aged 6-18 years recruited from four independent studies. Logistic regression and linear regression were performed to examine associations. Meta-analyses were conducted to pool the results of the four independent studies. The C-allele carriers of rs2943650 showed a 29% higher risk of obesity than noncarriers (OR (95% CI) = 1.29 (1.05, 1.58), P = 0.02) and a 0.41 kg/m(2) increase in BMI (beta (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)<0.05). Compared with the physically active children (physical activity >= 1 h/d and sedentary behaviors <2 h/d), the risk allele (C) of rs2943650 was significantly associated with a 241% increased risk of obesity among inactive children who participated in physical activity <1 h/d and sedentary behaviors >= 2 h/d (OR (95% CI) = 3.41 (1.45, 8.01), P = 0.005). Conclusions: We found that IRS1 rs2943650 was significantly associated with BMI and risk of childhood obesity. Additionally, 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. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.