Yang Yang, Gao XiangHui, Tao XiuJuan, Gao QingHan, Zhang YuHong, Yang JianJun
School of Public Health, Ningxia Medical University, Ningxia, China.
School of Public Health, Qingdao University, Shandong, China.
Asia Pac J Clin Nutr. 2019;28(1):177-182. doi: 10.6133/apjcn.201903_28(1).0023.
Fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes associated with obesity have been identified through Genome-wide Association Studies. However, no multiple loci interaction studies have been conducted in the Chinese population. This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China.
A total of 370 subjects (170 overweight/obese and 200 normal BMI subjects according to the Working Group on Obesity in China criteria) were enrolled using the random sampling method. FTO rs9939609 and rs9935401 and MC4R rs12970134 and rs17782313 interactions were analysed through generalized multifactor dimensionality reduction, and logistic regression models were used to calculate the risk of the relationship between genotypes and obesity.
Generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction among FTO rs9939609/MC4R rs12970134/MC4R rs17782313, with a score of 10/10 for the cross-validation consistency and 9 for the sign test (p=0.011). A 2.453-fold increased risk of obesity was observed in individuals carrying the genotypes of FTO rs9939609 TA/AA, MC4R rs12970134 GA/AA, and MC4R rs17782313 TC/CC (adjusted for age, sex, and ethnicity; 95% CI=1.12-5.37, p=0.025).
Our results suggested that FTO rs9939609, MC4R rs12970134, and MC4R rs17782313 are strongly associated with obesity. The combined effects were highly significant on obesity in children and adolescents living in Northwest China.
通过全基因组关联研究已确定了与肥胖相关的脂肪量和肥胖相关基因（FTO）以及黑皮质素4受体（MC4R）基因。然而，尚未在中国人群中开展多位点相互作用研究。本研究调查了FTO和MC4R的联合作用是否会增加中国西北地区儿童和青少年肥胖的风险。
采用随机抽样方法共纳入370名受试者（根据中国肥胖问题工作组标准，170名超重/肥胖者和200名BMI正常者）。通过广义多因素降维分析FTO rs9939609和rs9935401以及MC4R rs12970134和rs17782313的相互作用，并使用逻辑回归模型计算基因型与肥胖之间关系的风险。
广义多因素降维分析显示FTO rs9939609/MC4R rs12970134/MC4R rs17782313之间存在显著的基因-基因相互作用，交叉验证一致性得分为10/10，符号检验得分为9（p = 0.011）。携带FTO rs9939609 TA/AA、MC4R rs12970134 GA/AA和MC4R rs17782313 TC/CC基因型的个体肥胖风险增加2.453倍（根据年龄、性别和种族进行调整；95% CI = 1.12 - 5.37，p = 0.025）。
我们的结果表明FTO rs9939609、MC4R rs12970134和MC4R rs17782313与肥胖密切相关。联合作用对中国西北地区儿童和青少年的肥胖具有高度显著影响。
