Original Article

International Journal of Obesity (2007) 31, 1437–1441; doi:10.1038/sj.ijo.0803609; published online 13 March 2007

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

E H Young1, N J Wareham1, S Farooqi2, A Hinney3, J Hebebrand3, A Scherag4, S O'Rahilly2, I Barroso5 and M S Sandhu1,6

  1. 1MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK
  2. 2University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, UK
  3. 3Department of Child & Adolescent Psychiatry, Rheinische Kliniken Essen, University of Duisburg-Essen, Essen, Germany
  4. 4Institute of Medical Biometry & Epidemiology, Philipps-University of Marburg, Marburg, Germany
  5. 5Metabolic Disease Group, The Wellcome Trust Sanger Institute, Hinxton, UK
  6. 6Department of Public Health & Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK

Correspondence: Dr EH Young, MRC Epidemiology Unit, Medical Research Council, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK. E-mail: elizabeth.young@mrc-epid.cam.ac.uk

Received 30 October 2006; Revised 20 December 2006; Accepted 22 January 2007; Published online 13 March 2007.

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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.

Keywords:

genetics, MC4R, meta-analysis, polymorphism

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