Variants near MC4R associate with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes

  1. Dorit P. Zobel, MSc (dpaj{at}steno.dk)1,
  2. Camilla H. Andreasen, MSc1,
  3. Niels Grarup, MD1,
  4. Hans Eiberg, PhD2,
  5. Thorkild I.A. Sørensen, DMSc3,
  6. Annelli Sandbæk, PhD4,
  7. Torsten Lauritzen, DMSc4,
  8. Knut Borch-Johnsen, DMSc1,5,6,
  9. Torben Jørgensen, DMSc5,
  10. Oluf Pedersen, DMSc1,6,7 and
  11. Torben Hansen, PhD1,8
  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

    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, for association with obesity in 14,940 individuals, and for association with type 2 diabetes in 8,821 individuals.

    Results: The minor risk alleles of rs17782313, rs17700633, and rs12970134 associated with BMI (effect per-allele: 0.25 [P=0.01], 0.23 [P=0.01], and 0.31 [P=7×10−4] kg/m2, respectively); waist circumference (effect per-allele: 0.67 [P=0.006], 0.53 [P=0.02], and 0.85 [P=3×10−4] cm, respectively); and body weight (effect per-allele: 1.04 [P=6×10−4], 0.71 [P=0.01], and 1.16 [P=8×10−5] kg, respectively). In case-control studies of obesity defined by BMI the minor C-allele of rs17782313 associated with overweight/obesity and obesity (ORoverweight/obesity=1.09, P=0.006; ORobesity=1.12, P=0.003). Similarly, the minor A-allele of rs17700633 associated with overweight/obesity and obesity (ORoverweight/obesity=1.12, P=8×10−5; ORobesity=1.16, P=2×10−5), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (ORoverweight/obesity=1.13, P=2×10−5; ORobesity=1.15, P=6×10−5). rs477181, rs502933, and rs4450508 were not statistically significantly associated with obesity in the Danish population.

    Results: The frequency of the minor risk alleles of rs17782313 and rs12970134 were higher among patients with type 2 diabetes compared with glucose-tolerant individuals (OR=1.08, P=0.08; and OR=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

      • Received May 7, 2008.
      • Accepted December 4, 2008.

    This Article

    1. Published online before print December 10, 2008, doi: 10.2337/db08-0620
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