西安市30~36月龄幼儿肥胖遗传度及4个SNPs位点多态性分析

Heritability of obesity in children aged 30-36 months and an analysis of single nucleotide polymorphisms at four loci in Xi’an,China

目的分析西安市30~36月龄幼儿肥胖遗传度,探讨4个与体重指数相关的基因单核苷酸多态性(SNPs)位点在幼儿肥胖易感性中的作用。方法选取2017年3月至2018年12月在西安市随机抽样的4个社区的30~36月龄幼儿1637例为研究对象,对幼儿行体格测评,对家长进行问卷调查,用Falconer回归法计算幼儿肥胖的遗传度。共收集到297例行血生化检查幼儿的静脉血样本,其中肥胖/超重儿140例(肥胖/超重组),正常体重儿157例(正常体重组)。应用MassARRAY RS1000分型技术对CDKAL1基因rs2206734、KLF9基因rs11142387、PCSK1基因rs261967和GP2基因rs12597579位点进行检测,比较肥胖/超重组与正常体重组幼儿等位基因、基因型的分布差异,进一步用非条件logistic回归模型分析显性、隐性遗传模型效益。结果1637例幼儿中,肥胖双亲的遗传度为83%±8%,源于母亲的遗传度为86%±11%,略高于源于父亲的78%±12%。rs2206734位点等位基因和基因型、rs261967位点基因型分布在肥胖/超重组和正常体重组幼儿间比较差异有统计学意义(P<0.0125);rs2206734携带T等位基因的个体肥胖的风险低于纯合子CC个体(OR=0.24,P<0.0125);rs261967纯合子GG个体肥胖的风险显著高于携带A等位基因的个体(OR=4.11,P<0.0125)。结论遗传因素在幼儿肥胖发病中起重要作用;CDKAL1基因rs2206734和PCSK1基因rs261967位点SNPs和西安市30~36月龄幼儿肥胖易感性相关。

Objective To study the heritability of obesity in children aged 30-36 months in Xi’an,China,as well as the role of four single nucleotide polymorphisms(SNPs)associated with body mass index in the susceptibility to obesity in children.Methods Random sampling was performed to select 1637 children,aged 30-36 months,from four communities of Xi’an from March 2017 to December 2018.Physical assessment was performed for these children,and a questionnaire survey was conducted for parents.Then the Falconer regression method was used to calculate the heritability of childhood obesity.Venous blood samples were collected from 297 children who underwent biochemical examinations,among whom there were 140 children with obesity/overweight(obesity/overweight group)and 157 with normal body weight(normal body weight group).The MassARRAY RS1000 typing technique was used to detect CDKAL1 gene rs2206734,KLF9 gene rs11142387,PCSK1 gene rs261967,and GP2 gene rs12597579.The distribution of alleles and genotypes was compared between the obesity/overweight and normal body weight groups.An unconditional logistic regression model was used to investigate the benefits of dominant and recessive genetic models.Results For the 1637 children,the heritability of obesity from the parents was 83%±8%,and the heritability from mother was slightly higher than that from father(86%±11%vs 78%±12%).There were significant differences in the distribution of rs2206734 alleles and genotypes and rs261967 genotypes between the obesity/overweight and normal body weight groups(P<0.0125).The children carrying T allele at rs2206734 had a significantly higher risk of obesity than those carrying CC(OR=0.24,P<0.0125),and the children carrying GG at rs261967 had a significantly higher risk of obesity than those carrying A allele(OR=4.11,P<0.0125).Conclusions Genetic factors play an important role in the pathogenesis of obesity in children,and the SNPs of CDKAL1 rs2206734 and PCSK1 rs261967 are associated with the susceptibility to obesity in children aged 30-36 months in Xi’an.