Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure

• Published in: International Journal of Obesity 2010-01, Vol.34 (1), p.182-189
• Main Authors: Kring, S.I.I, Holst, C, Toubro, S, Astrup, A, Hansen, T, Pedersen, O, Sørensen, T.I.A
• Format: Article
• Language: English
• Subjects: Abdomen; Adolescent; Adolescents; Adult; Age; Alleles; Allelomorphism; Biological and medical sciences; Body fat; Body Fat Distribution; Body Mass Index; Body measurements; Body weight; Children; Cholesterol; Cholesterol, HDL - blood; Cholesterol, HDL - genetics; Denmark - epidemiology; Diabetes mellitus (non-insulin dependent); Energy; Energy distribution; Energy expenditure; Energy Metabolism - genetics; Epidemiology; General aspects; Genetic aspects; Genetic Variation - genetics; Genomes; Genotype; Health aspects; Health Promotion and Disease Prevention; High density lipoprotein; Hospitals; Humans; Insulin; Internal Medicine; Leptin; Male; Medical sciences; Medicine; Medicine & Public Health; Melanocortin; Melanocortin MC4 receptors; melanocortin receptor 4; men; Metabolic Diseases; Metabolism; Middle Aged; Miscellaneous; Nutrition; Obesity; Obesity - blood; Obesity - epidemiology; Obesity - genetics; Obesity - physiopathology; Obesity in children; original-article; Phenotype; Polls & surveys; Preventive medicine; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Receptor, Melanocortin, Type 4 - genetics; receptors; Regression analysis; Standard scores; Surveys; weight gain; Young Adult
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2009.215

Objective: Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure. Methods: Obese young men (n=753, BMI > or = 31.0 kg m-2) and a randomly selected group (n=874) identified from a population of 174 800 men were re-examined in three surveys at mean ages 35, 46 and 49 years (S-35, S-46 and S-49). Measurements were available at upto eight times from birth to adulthood. Logistic regression analysis was used to assess odds ratio (OR) for the presence of the carrier allele for a given difference in phenotypic values. Results: Rs17782313 minor C-allele was associated with overall, abdominal and peripheral fatness (range of OR=1.06-1.14 per z-score units) at all three surveys, although only consistently significant at S-35 and S-46. Rs17700633 minor A-allele was also associated with the fatness measures, but significantly so only at S-49 for overall and abdominal fatness (range of OR=1.03-1.15 per z-score units), and peripheral fatness (OR=1.15-1.20 per z-score units). There were only few significant associations with metabolic traits. The rs17782313 C-allele and the rs17700633 A-allele were both associated with lower high-density lipoprotein cholesterol (range of OR=0.64-0.84 per mol l-1), significantly at S-46. The rs17700633 A-allele was significantly associated with insulin (OR=1.25 per 50 pmol l-1), leptin (OR=1.42 per 10 ng microliter-1) and insulin sensitivity (OR=0.81 per model unit). The rs17782313 C-allele and the rs17700633 A-allele were both associated with BMI in childhood and adolescence (range of OR=1.04-1.17 per z-score units), significant for the rs17782313 C-allele at the age of 13-19 years and for rs17700633 A-allele at age 7, 10, 13 and 19 years. No significant associations were found for energy expenditure. Conclusion: Near MC4R variants appear to contribute to body fat, body fat distribution, some metabolic traits, weight development during childhood, but not to energy expenditure.