Abstract
Effects of MC4R variants in previous Chinese population studies were inconsistent. Gene-environment interactions might influence the effect of MC4R variants on obesity, which was still unclear. We performed the study to clarify the association of variants near MC4R gene with obesity-related phenotypes and gene-environment interactions in Chinese children and adolescents. Two common variants (rs12970134 and rs17782313) near MC4R were genotyped in 2179 children and adolescents aged 7–18 years in Beijing of China. Associations between the variants and obesity-related phenotypes together with gene-environment interactions were analyzed. The A-alleles of rs12970134 were nominally associated with risk of overweight/obesity (Odds Ratios (OR) = 1.21, 95%CI: 1.03–1.44, P = 0.025) and BMI (β = 0.33 kg/m2, 95%CI: 0.02–0.63, P = 0.025), respectively. The rs12970134 was also associated with HDL-C (β = -0.03mmol/L per A-allele, 95%CI: -0.05, -0.01, P = 0.013) independent of BMI. In the further analysis, we found the significant interaction of rs12970134 and physical activity/sedentary behaviors on BMI (Pinteraction = 0.043). The rs12970134 was found to be associated with BMI only in children with physical activity<1h/d and sedentary behaviors ≥2h/d (BMI: β = 1.27 kg/m2, 95%CI: 0.10–2.45, P = 0.034). The association was not detected in their counterparts with physical activity≥1h/d or sedentary behaviors <2h/d. We identified the effect of MC4R rs12970134 on overweight/obesity and BMI, and we also found physical activity and sedentary behaviors modified the association between the rs12970134 and BMI in Chinese children and adolescents.
Highlights
The melanocortin-4 receptor (MC4R) is primarily expressed in the central nervous system and a part of melanocortinergic pathway that regulates food intake and controls energy homeostasis [1]
We investigated the combined effect of physical activity, sedentary behaviors and MC4R variants on body mass index (BMI) and risk of overweight/obesity
In stratified subgroups of different level of physical activity or sedentary behaviors, we only found the risk A-allele of rs12970134 variant was marginally associated with increased BMI in children who participated in sedentary behaviors!2h/day (β = 0.74kg/m2, 95%CI: 0.01–1.47, P = 0.048, Table 4)
Summary
The melanocortin-4 receptor (MC4R) is primarily expressed in the central nervous system and a part of melanocortinergic pathway that regulates food intake and controls energy homeostasis [1]. The effect of rs17782313 on BMI in children was about twice of that observed in adults, indicating rs17782313 was relevant to early-onset obesity. Another GWAS in adults of Indian Asian and European descent found that a common SNP rs12970134 at 154 kb downstream of MC4R was associated with waist circumference and insulin resistance [5]. The associations of rs17782313 or rs12970134 with obesity-related phenotypes were confirmed by several subsequent studies in different ethnicity and age groups [6,7,8,9,10,11,12,13,14] It is not consistent in Chinese population. Despite some studies showed evidence of significant association (Shi et al [7] and Huang et al [15] in adults; Hong et al [16] in young, Wu et al [8] in children), studies by Cheung et al [17] and Tao et al [18] in adults, Wang et al [19] in children revealed non-significant association
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