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

International Journal of Obesity volume 31, pages 1437–1441 (2007)Cite this article

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.

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Acknowledgements

We gratefully acknowledge the support of corresponding authors:

Dr C Bouchard, Dr P Jacobson, Dr RJF Loos Human Genomics Laboratory, Pennington Biomedical Research Center, USA; Dr IM Heid, Dr T Illig GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany; Professor Winfried Rief Department of Psychology, Philipps-University of Marburg, Germany; Professor S Herpertz Department for Psychosomatic Medicine and Psychotherapy, Westfälisches Zentrum for Psychiatry, Psychotherapy and Psychosomatics, Dortmund, Germany; Dr M Laakso, Dr J Pihlajamäki Department of Medicine, University of Kuopio, Finland; Dr F Santini Department of Endocrinology and Metabolism, University of Pisa, Italy.

Deborah Smyth and John Todd with Juvenile Diabetes Research Foundation and Wellcome Trust funding are thanked for genotyping some of the EPIC samples. Genotyping of additional German samples was funded by the German National Genome Net-2.

The analyses in this paper were conducted as part of the Genes in Energy Balance and Metabolism (GEM) Consortium between the MRC Epidemiology Unit, the Sanger Institute and University of Cambridge. The MRC Ely Study is supported by the MRC and the EPIC-Norfolk Study by programme grants from the MRC and CRUK with additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency and the Wellcome Trust. IB is funded by The Wellcome Trust. SO'R, IB and JH acknowledge support from EU FP6 funding (contract no. LSHM-CT-2003–503041). EHY is an MRC Career Development Fellow.

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Authors and Affiliations

  1. MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK

    E H Young, N J Wareham & M S Sandhu

  2. University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, UK

    S Farooqi & S O'Rahilly

  3. Department of Child & Adolescent Psychiatry, Rheinische Kliniken Essen, University of Duisburg-Essen, Essen, Germany

    A Hinney & J Hebebrand

  4. Institute of Medical Biometry & Epidemiology, Philipps-University of Marburg, Marburg, Germany

    A Scherag

  5. Metabolic Disease Group, The Wellcome Trust Sanger Institute, Hinxton, UK

    I Barroso

  6. Department of Public Health & Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK

    M S Sandhu

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Correspondence to E H Young.

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Young, E., Wareham, N., Farooqi, S. et al. The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. Int J Obes 31, 1437–1441 (2007). https://doi.org/10.1038/sj.ijo.0803609

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