肥胖相关基因多态性对儿童期肥胖发生风险及持续状态的影响

赵小元; 张美仙; 程红; 闰银坤; 吴丽君; 沈明; 米杰

Abstract

赵小元,张美仙,程红,闰银坤,吴丽君,沈明,米杰.肥胖相关基因多态性对儿童期肥胖发生风险及持续状态的影响[J].Chinese journal of Epidemiology,2013,34(6):560-565

肥胖相关基因多态性对儿童期肥胖发生风险及持续状态的影响

Risk of obesity-related gene polymorphism on the incidence and durative of childhood obesity

Received:January 07, 2013 Revised:June 23, 2012

DOI：

KeyWord: 肥胖基因单核苷酸多态性随访儿童期

English Key Word: Obesity Gene Single nucleotide polymorphism Follow up Childhood

FundProject:国家重点基础研究发展计划(973计划);国家"十二五"科技支撑计划，北京市科技计划重点项目

Author Name	Affiliation	E-mail
ZHAO Xiao-yuan	Department of Epidemiology, Capital Institute of Pediatric,Beijing 100020,China	jiemi@vip.163.com
ZHANG Mei-xian	Graduate School Medical College
CHENG Hong	Department of Epidemiology, Capital Institute of Pediatric,Beijing 100020,China
YAN Yin-kun	Department of Epidemiology, Capital Institute of Pediatric,Beijing 100020,China
WU Li-jun	Department of Epidemiology, Capital Institute of Pediatric,Beijing 100020,China
SHEN Yue	Department of Epidemiology, Capital Institute of Pediatric,Beijing 100020,China
MI Jie	Graduate School Medical College

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Abstract:

目的前瞻性分析肥胖相关基因多态性对儿童期肥胖发生及持续状态的影响.方法基于北京市儿童青少年代谢综合征(BCAMS)研究,对部分仍在校者进行6年后随访,测量身高和体重,以随访到的780名儿童青少年为研究对象.采用盐析法从外周血白细胞中提取DNA.通过查阅文献和专家研讨,确定6个基因的7个多态性位点(SNP),其中FTO rs9939609分型使用ABI-5700实时定量PCR仪,其他6个SNP位点(FTO rs6499640、FAIM2 rs7138803、NPCIrs1805081、MC4R rs 17782313、BDNF rs6265、GNPDA2 rs10938397)的分型使用ABI PrismsTM-7900实时荧光定量PCR仪.采用中国肥胖问题工作组推荐的BMI分类标准判定超重和肥胖.计量资料组间比较采用独立样本t检验,分类资料组间比较采用x2检验.采用多因素logistic回归分析肥胖相关基因多态性对儿童期肥胖发生风险和持续状态的影响.结果随访6年肥胖累积发病率为8.5%,基线肥胖的儿童青少年有65.1%随访6年后仍持续肥胖.FTO rs9939609基因型TT、TA和AA组肥胖发病率依次升高(趋势检验x2=8.030,P<0.05)；控制随访时点年龄、性别和城乡居住地后,携带FTO rs9939609A等位基因者相对于无该等位基因者发生肥胖的OR值及95%CI为2.42(1.31 ～ 4.47).与基线非肥胖且不携带rs9939609A等位基因组比较,携带rs9939609A等位基因组、基线肥胖组、基线肥胖同时携带rs9939609 A危险等位基因组随访时点罹患肥胖的风险分别为OR=2.07 (95% CI:0.95 ～ 4.47)、OR=22.01 (95%CI:13.27 ～ 36.49)和OR=45.95 (95%CI:24.00～87.94).其他SNP与肥胖的关联无统计学意义(P>0.05).综合分析多个SNP的共同效应发现,遗传危险得分每增加1个单位,肥胖的发病风险增加16.42倍(95%CI:3.59～75.10,P<0.001).结论FTO rs9939609对儿童期新发肥胖及肥胖的持续状态都具有一定影响.多个肥胖相关基因的综合效应对肥胖发病的影响不可忽视.

English Abstract:

Objective To examine the impact of single nucleotide polymorphisms (SNPs) in obesity-related genes on the incidence and durative of obesity in childhood and adolescence.Methods Based on the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study,780 school children aged 6 to 16 years were followed-up in 2010,and assessed for body size parameters.Venipuncture blood samples were collected after a 12-hour overnight fast.Genomic DNA was isolated from peripheral blood white cells under the salt fractionation method.SNPs were genotyped by ABI 5700 real time PCR (FTO rs9939609) and TaqMan Allelic Discrimination Assays with the GeneAmp 7900 Sequence Detection System (Applied Biosystems,Foster City,CA,USA) (FTO rs6499640,FAIM2 rs7138803,NPC1 rs1805081,MC4R rs17782313,BDNF rs6265,GNPDA2 rs10938397).Both overweight and obesity were diagnosed by the Chinese age-and sex-specific body mass index (BMI)cutoffs.Two independent sample t-test,Chi-square test and multiple logistic regression analysis were performed.Results During the 6 years follow-up period,the incidence of obesity in the total sample 8.5%,and 65.1% individuals had persisted their obese status.The genotypes of the SNPs except BDNF rs6265 were in Hardy-Weinberg equilibrium in each group (P>0.05).The incidence rates of obesity increased with FTO rs9939609 TT,TA and AA genotypes (x2 for trend=8.030,P<0.05).In the non-obese sub-cohort,after adjusted for sex,age at the initial time of follow up and residential area,when compared with children carrying FTO rs9939609 T-allele,a significantly relative risk of obesity was observed for children carrying the rs9939609 A-allele (OR=2.42,95%CI:1.31-4.47,P=0.005).In the obese sub-cohort,FTO rs9939609 A-allele was significantly associated with durative of obesity (OR=1.72,95%CI:1.07-2.77,P=0.026).However,no statistical significant associations were seen between other SNPs (FTO rs6499640,FAIM2 rs7138803,NPCI rs1805081,MC4R rs17782313,GNPDA2 rs10938397) and the incidence or durative of obesity (all P>0.05).The genetic risk scorewas associated with the risk of occurrence of obesity (OR=16.42,95% CI:3.59-75.10,P<0.001)after adjusted for residential area,sex,age at the initial time of follow up and baseline BMI.Conclusion We confirmed the association of FTO rs9939609 with incidence and durative of obesityin children.Early intervention was recommended on the high risk individuals who carrying more riskalleles in obesity-related genes.

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