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1.  The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals 
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 8,304 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% CI 4-30%, p=0·015) lower risk of obesity compared with noncarriers. 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.
doi:10.1038/sj.ijo.0803609
PMCID: PMC2683751  PMID: 17356525

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