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

Dorit P. Zobel, Camilla H. Andreasen, Niels Grarup, Hans Eiberg, Thorkild I.A. Sørensen, Annelli Sandbaek, Torsten Lauritzen, Knut Borch-Johnsen, Torben Jørgensen, Oluf Pedersen, Torben Hansen

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    Abstrakt

    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.

    OriginalsprogEngelsk
    Sider (fra-til)757-764
    Antal sider8
    TidsskriftDiabetes
    Vol/bind58
    Udgave nummer3
    DOI
    StatusUdgivet - 1 mar. 2009

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