Genetic variants in the MC4R gene and risk of obesity/overweight: A systematic review and meta-analysis.

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-04-30 DOI:10.1111/dom.16425

Sara Cheraghi, Tofigh Mobaderi, Azadeh Mottaghi, Fatemeh Movahedi Motlagh, Sara Taghizadeh, Maryam Eghbali

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引用次数: 0

Abstract

Aim: Obesity is a significant health issue worldwide, progressing due to genetic factors and lifestyle. Melanocortin 4 receptor (MC4R) gene polymorphisms have been identified as a cause of overweight and obesity risk. The aim of this study was a comprehensive assessment of MC4R polymorphism effects on overweight/obesity risk.

Methods: All retrieved literature from PubMed, Web of Science and Scopus according to PRISMA guidelines up to June 2022 was reviewed. Inclusion criteria are restricted to English-language, human case-control/cohort studies with genotype distributions of MC4R polymorphisms and their association with obesity and overweight in any geographic regions and age. The heterogeneity using the I-squared statistic (I²), the Q-test and Prediction Interval (PI) and publication bias using Begg's and Egger's tests were examined, and the pooled odds ratios in different genetic models were estimated using a random effect model. Subgroup analysis was performed by the geographic regions and age groups. Risk of bias for individual studies was not assessed. The review is limited by restricted racial diversity and exclusion of environmental factors, incomplete data and limited access to certain articles. This work received no specific funding, and the review was not prospectively registered.

Results: In our study, 39 eligible studies with 43 697 overweight and obese cases and 52 272 normal weights were included. In mixed-age populations, rs17700633, rs17782313, rs11872992, rs12970134, rs2229616 and rs571312 were evaluated. The remarkable association was seen by rs17782313 and rs12970134 in the Homozygous model (OR = 1.73; 95% CI: 1.51, 1.98 and 1.74; 95% CI: 1.29; 2.35, respectively). In addition, rs17782313 and rs12970134 were found to be more strongly linked to overweight and obesity in Asian and European population groups, as determined by a subgroup analysis of the geographic regions.

Conclusion: The present study confirms the high association of rs17782313 and rs12970134 with obesity and overweight in all age groups and geographic regions. However, further functional studies and high-population research on other MC4R SNPs must validate their role.

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MC4R基因的遗传变异与肥胖/超重的风险：一项系统综述和荟萃分析

目的：肥胖是一个全球性的重大健康问题，由于遗传因素和生活方式的发展。黑素皮质素4受体（MC4R）基因多态性已被确定为超重和肥胖风险的原因。本研究的目的是全面评估MC4R多态性对超重/肥胖风险的影响。方法：根据PRISMA指南检索PubMed、Web of Science和Scopus截至2022年6月的所有文献。纳入标准仅限于英语、人类病例对照/队列研究，这些研究具有MC4R多态性的基因型分布及其与任何地理区域和年龄的肥胖和超重的关联。采用i平方统计量（I2）、q检验和预测区间（PI）以及Begg’s和Egger’s检验检验发表偏倚的异质性，并采用随机效应模型估计不同遗传模型的合并优势比。按地理区域和年龄组进行亚组分析。未对个别研究的偏倚风险进行评估。由于受限制的种族多样性和排除环境因素、数据不完整和获取某些文章的机会有限，审查受到限制。这项工作没有获得特定的资助，并且该综述没有前瞻性注册。结果：在我们的研究中，纳入39项符合条件的研究，43 697例超重和肥胖病例，52 272例正常体重。在混合年龄人群中，对rs17700633、rs17782313、rs11872992、rs12970134、rs2229616和rss571312进行评价。rs17782313和rs12970134在纯合模型中表现出显著的相关性(OR = 1.73；95% CI: 1.51、1.98和1.74；95% ci: 1.29；分别为2.35)。此外，rs17782313和rs12970134在亚洲和欧洲人群中与超重和肥胖的关联更强，这是由地理区域的亚组分析确定的。结论：本研究证实了rs17782313和rs12970134与肥胖和超重在所有年龄组和地理区域的高度相关。然而，其他MC4R snp的进一步功能研究和高群体研究必须验证它们的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.