Variants Near MC4R Are Associated With Obesity and Influence Obesity-Related Quantitative Traits in a Population of Middle-Aged People: Studies of 14,940 Danes

  1. Dorit P. Zobel1,
  2. Camilla H. Andreasen1,
  3. Niels Grarup1,
  4. Hans Eiberg2,
  5. Thorkild I.A. Sørensen3,
  6. Annelli Sandbæk4,
  7. Torsten Lauritzen4,
  8. Knut Borch-Johnsen156,
  9. Torben Jørgensen5,
  10. Oluf Pedersen167 and
  11. Torben Hansen18
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark
  3. 3Institute of Preventive Medicine, Copenhagen University Hospital, Center for Health and Society, Copenhagen, Denmark
  4. 4Department of General Practice, University of Aarhus, Aarhus, Denmark
  5. 5Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  6. 6Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  7. 7Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
  8. 8Faculty of Health Science, University of Southern Denmark, Odense, Denmark
  1. Corresponding author: Dorit Packert Zobel, dpaj{at}steno.dk

Abstract

OBJECTIVE— Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals.

RESEARCH DESIGN AND METHODS— The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based sampled individuals, obesity in 14,940 individuals, and type 2 diabetes in 8,821 individuals.

RESULTS— The minor risk alleles of rs17782313, rs17700633, and rs12970134 were associated with BMI (effect per allele 0.25 kg/m2, P = 0.01; 0.23, P = 0.01; and 0.31, P = 7 × 10−4, respectively), waist circumference (0.67 cm, P = 0.006; 0.53, P = 0.02; and 0.85, P = 3 × 10−4), and body weight (1.04 kg, P = 6 × 10−4; 0.71, P = 0.01; and 1.16, P = 8 × 10−5). In case-control studies of obesity defined by BMI, the minor C-allele of rs17782313 was associated with overweight/obesity and obesity (odds ratio [OR] 1.09, P = 0.006 and OR 1.12, P = 0.003, respectively). Similarly, the minor A-allele of rs17700633 was associated with overweight/obesity and obesity (1.12, P = 8 × 10−5 and 1.16, P = 2 × 10−5), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (1.13, P = 2 × 10−5 and 1.15, P = 6 × 10−5). rs477181, rs502933, and rs4450508 were not significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 was higher among patients with type 2 diabetes than among glucose-tolerant individuals (OR 1.08, P = 0.08 and 1.08, P = 0.06, respectively); however, these borderline associations were abolished after adjustment for BMI.

CONCLUSIONS— rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 10 December 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 4, 2008.
    • Received May 7, 2008.
| Table of Contents

This Article

  1. Diabetes vol. 58 no. 3 757-764
  1. Online-Only Appendix
  2. All Versions of this Article:
    1. db08-0620v1
    2. 58/3/757 most recent