FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.
FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.
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DOI：
10.1136/bmj.i4707
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Mathers JC
中科院分区：
文献类型：
--
作者：
Livingstone KM;Celis-Morales C;Papandonatos GD;Erar B;Florez JC;Jablonski KA;Razquin C;Marti A;Heianza Y;Huang T;Sacks FM;Svendstrup M;Sui X;Church TS;Jääskeläinen T;Lindström J;Tuomilehto J;Uusitupa M;Rankinen T;Saris WH;Hansen T;Pedersen O;Astrup A;Sørensen TI;Qi L;Bray GA;Martinez-Gonzalez MA;Martinez JA;Franks PW;McCaffery JM;Lara J;Mathers JC
目的 在随机对照试验中评估 FTO 基因型对饮食、体力活动或药物干预后体重减轻的影响。设计对随机对照试验中的个体参与者数据进行系统审查和随机效应荟萃分析。数据来源：Ovid Medline、Scopus、Embase 和 Cochrane，从开始到 2015 年 11 月。 研究选择的资格标准 对超重或肥胖成年人进行的随机对照试验，报告在饮食、体力活动或基于药物的干预措施后，FTO 基因型（rs9939609 或代理）的体重指数、体重或腰围有所减少。使用遗传效应的等位基因剂量编码和一组通用的协变量，将基因治疗相互作用模型与本综述中所有研究的个体参与者数据进行拟合。使用随机效应模型组合研究水平的相互作用。元回归和亚组分析用于评估研究异质性的来源。结果我们确定了八项符合条件的随机对照试验进行系统评价和荟萃分析 (n=9563)。总体而言，FTO 基因型之间体重指数、体重和腰围响应减肥干预的差异变化没有显着差异。敏感性分析表明，FTO 基因型导致的体重指数、体重和腰围的差异变化并不因干预类型、干预长度、种族、样本量、性别、基线体重指数和年龄类别而异。结论 我们观察到，FTO 小等位基因的携带与减肥干预后肥胖的差异变化无关。这些发现表明，携带次要等位基因的个体对饮食、体力活动或基于药物的减肥干预措施的反应同样良好，因此与 FTO 次要等位基因相关的肥胖遗传倾向可以通过此类干预措施至少部分抵消。系统审核注册 PROSPERO CRD42015015969。
Objective To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. Design Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. Data sources Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. Eligibility criteria for study selection Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. Results We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. Conclusions We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. Systematic review registration PROSPERO CRD42015015969.
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