The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals

Abstract

Background: Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation.

Methods: We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8304 individuals. We also did a meta-analysis of relevant studies, involving 10 975 cases and 18 588 controls, to place our findings in context.

Finding: In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% confidence interval 4-30%, P=0.015) lower risk of obesity compared with non-carriers. There was no heterogeneity among studies and no apparent publication bias.

Interpretation: This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential.

Figure 1. Meta-analysis of studies of MC4R V103I polymorphism and obesity

^†Received by personal correspondence with authors. ^~Data from the Swedish Obesity Study only. ^*Includes additional data from the HERITAGE Family Study, unrelated parents only: a, Whites; b, Blacks. ^‡Data presented only for the Essen cohort from Geller, 2004; the Ausburg (KORA) cohort has been omitted and superseded by the KORA surveys published in Heid, 2005. ^≫Quebec Family Study: parent data only. ^$Supersedes earlier publications and includes additional unpublished data (available from corresponding author on request). ^μResult based on a re-analysis of raw data with inclusion of additional unpublished data (available from corresponding author on request) and supersedes earlier publications.​ - ^#Total excludes three studies with 0 carriers in one group and OR could not be calculated.