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Genetic Variants in the Mc4r Gene and Risk of Obesity/Overweight: A Systematic Review and Meta-Analysis Publisher



Cheraghi S1 ; Mobaderi T2 ; Mottaghi A3 ; Movahedi Motlagh F4 ; Taghizadeh S5 ; Eghbali M1
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Authors Affiliations
  1. 1. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Research Center for Prevention of Cardiovascular Diseases, Endocrinology & Metabolism, Institute of Endocrinology Metabolism, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Translational Ophthalmology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Diabetes, Obesity and Metabolism Published:2025


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. © 2025 John Wiley & Sons Ltd.
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