Association of MC4R rs17782313 Genotype With Energy Intake and Appetite: A Systematic Review and Meta-analysis

The melanocortin-4 receptor gene (MC4R) is associated with a higher risk of obesity by the presence of the C allele in rs17782313, but the mechanisms are not clear.

The present systematic review and meta-analysis aimed to explore the association between the different genotypes of MC4R rs17782313 and energy intake and appetite.

A literature search was conducted up to June 2023 in PubMed, Scopus, Web of Science, and Cochrane Collaboration databases, following PRISMA guidelines.

Inclusion criteria were studies in humans measuring energy intake, appetite, or satiety in all ages and physiological conditions. Studies dealing solely with body mass index were excluded. Twenty-one articles representing 48 560 participants were included in the meta-analysis.

According to the NHLBI (National Heart, Lung, and Blood Institute) quality-assessment criteria, all case-control studies and 6 out of 17 cohort and cross-sectional studies were classified as "good," while the rest scored as "fair." Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in a (CT+CC) vs TT dominant model, and both random-effects and fixed-effects models were used. A statistically significant association between the presence of the C allele and increased appetite was found (OR = 1.25; 95% CI: 1.01-1.49; P = .038) using the fixed-effects model, but the random-effects model proved nonsignificant. However, no association with energy intake was found. None of the variables considered (sample size, year of publication, sex, age group, type of population, origin, and quality) were identified as effect modifiers, and no publication biases were found after subgroup and meta-regression analyses.

To our knowledge, this is the first systematic review and meta-analysis that has analyzed the association between rs17782313 of MC4R and energy intake and appetite. Identifying people genetically predisposed to increased appetite may be of great interest, not only to prevent obesity in younger populations but also to avoid malnutrition in elderly persons. This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.

PROSPERO registration no. CRD42023417916.