Koya Charita, Yu Tsung, Strong Carol, Tsai Meng-Che
1 Faculty of Health Sciences, University of Ottawa , Ottawa, Ontario, Canada .
2 Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University , Tainan, Taiwan .
Child Obes. 2018 May/Jun;14(4):218-226. doi: 10.1089/chi.2017.0265. Epub 2018 Apr 24.
Two common missense variants in the melanocortin-3 receptor (MC3R) gene, Thr6Lys (T6K) and Val81Ile (V81I), are presumably correlated with pediatric obesity. This meta-analysis aimed to examine and synthesize evidence on the association between these two common MC3R polymorphisms and the development of childhood obesity.
A combination of words relevant to the research question was searched on PubMed, EMBASE, Scopus, and the Cochrane database. Results were restricted to human studies, specifically child and adolescent populations. Articles were excluded based on accessibility of full online texts and availability of pertinent data. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model to determine the association of the polymorphisms with obesity.
Searches on the databases using the keywords identified 65 potentially relevant reports. Among them, 32 studies were excluded due to irrelevance, and 28 studies excluded due to lack of access, insufficient data, and investigation of other variants. A final set of five studies included in this meta-analysis found that the risk of overweight/obesity increased by 46.1% per K allele and 21.7% per I allele. Only homozygous genotypes for T6K were associated with a 3.10-fold (95% CI: 1.29-7.43) increased risk of overweight/obesity in children. Data were insufficient to examine if homozygosity for both rare alleles further increases risk.
Our results supported a recessive inheritance model for MC3R gene as a potential cause of childhood obesity. High clinical heterogeneity existed among studies and thus requires more research of larger participation for future integration of data.
黑皮质素-3受体（MC3R）基因中的两个常见错义变体，即苏氨酸6赖氨酸（T6K）和缬氨酸81异亮氨酸（V81I），可能与儿童肥胖有关。这项荟萃分析旨在检验和综合关于这两种常见MC3R基因多态性与儿童肥胖发展之间关联的证据。
在PubMed、EMBASE、Scopus和Cochrane数据库中搜索与研究问题相关的词汇组合。结果仅限于人类研究，特别是儿童和青少年人群。根据全文在线文本的可获取性和相关数据的可用性排除文章。使用随机效应模型计算合并比值比（OR）和95%置信区间（CI），以确定多态性与肥胖的关联。
使用关键词在数据库中搜索到65篇潜在相关报告。其中，32项研究因不相关被排除，28项研究因无法获取、数据不足和对其他变体的研究而被排除。本荟萃分析最终纳入的五项研究发现，每一个K等位基因超重/肥胖风险增加46.1%，每一个I等位基因增加21.7%。仅T6K的纯合基因型与儿童超重/肥胖风险增加3.10倍（95%CI：1.29 - 7.43）相关。数据不足以检验两种罕见等位基因的纯合性是否会进一步增加风险。
我们的结果支持MC3R基因的隐性遗传模型是儿童肥胖的潜在原因。研究之间存在高度临床异质性，因此需要更多大规模参与的研究以便未来整合数据。
