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Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys
  1. I M Heid1,
  2. C Vollmert1,
  3. A Hinney2,
  4. A Döring1,
  5. F Geller3,
  6. H Löwel1,
  7. H-E Wichmann1,
  8. T Illig1,
  9. J Hebebrand2,
  10. F Kronenberg1,1,4,
  11. the KORA Group
  1. 1GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
  2. 2Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Germany
  3. 3Institute of Medical Biometry and Epidemiology, Philipps-University of Marburg, Germany
  4. 4Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria
  1. Correspondence to:
 Dr T Illig
 GSF - National Research Center for Environment and Health, Institute of Epidemiology, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; illiggsf.de

Abstract

Background: The melanocortin-4-receptor gene (MC4R) is part of the melanocortinergic pathway that controls energy homeostasis. In a recent meta-analysis, the MC4R V103I (rs2229616) polymorphism was shown to be associated with body weight regulation. Although no functional differences between the isoleucine comprising receptor and the wild type receptor have been detected as yet, this meta-analysis of 14 case–control studies reported a mild negative association with obesity (odds ratio (OR) 0.69, p = 0.03). However, evidence in a large population based study in a homogeneous population and a significant estimate of the change in quantitative measures of obesity is still lacking.

Methods: We analysed the data of two surveys of a white population with the same high quality study protocol, giving a total of 7937 participants.

Results: By linear regression, we found a significant decrease of 0.52 body mass index (BMI) units (95% confidence interval (CI) −0.02 to −1.03, p = 0.043) for carriers of the heterozygote rs2229616G/A genotype, which was observed in 3.7% of the participants. Logistic regression yielded a significantly negative association of the MC4R variant with “above average weight” (BMI ⩾ median BMI) yielding an OR of 0.75 (95% CI 0.59 to 0.95 p = 0.017). We obtained similar results comparing obese (BMI ⩾30 kg/m2, World Health Organization results for 1997) with non-obese (BMI <30 kg/m2) participants. The results were found for both sexes and each survey separately, and did not depend on the modelling of age, sex, or survey effects.

Conclusions: Our study confirms previous findings of a meta-analysis that the relatively infrequent G/A genotype of the V103I MC4R polymorphism is negatively associated with above average weight and obesity in population based original data of 7937 participants, and extends previous findings by showing for the first time a significantly lower BMI in individuals carrying the infrequent allele of this MC4R variant.

  • MC4R
  • body mass index
  • population based survey
  • obesity

https://doi.org/10.1136/jmg.2004.027011

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    Footnotes

    • The KORA group consists of H-E Wichmann (speaker), H Löwel, C Meisinger, T Illig, R Holle, J John, and their coworkers, who are responsible for the design and conduct of the KORA studies. The MONICA Augsburg study was initiated and conducted by U Keil and coworkers. Our work was supported within the German National Genomic Research Network (NGFN) by the Federal Ministry of Education and Research (BMBF).

    • The first two authors contributed equally to this work.

    • Competing interests: none of the authors has in the past 5 years accepted any reimbursement for attending a symposium, any fee for speaking or for organising education, any funds for research or a member of staff, or any fee for consulting from an organisation that may in any way gain or lose financially from the results of our study or the conclusions of our manuscript, nor have they been employed by or hold any stocks or shares in such an organisation. None of the authors has acted as an expert witness on the subject of our study, and they have no other competing financial interests