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

Int J Obes (Lond). 2007 Sep;31(9):1437-41. doi: 10.1038/sj.ijo.0803609. Epub 2007 Mar 13.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Body Mass Index
  • Cohort Studies
  • Genetic Predisposition to Disease*
  • Genetics, Population
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Phenotype
  • Polymorphism, Genetic*
  • Receptor, Melanocortin, Type 4 / genetics*


  • Receptor, Melanocortin, Type 4