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

TY - JOUR

T1 - Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure

AU - Kring, Sofia Inez Iqbal

AU - Holst, C.

AU - Toubro, S.

AU - Astrup, Arne

AU - Hansen, T.

AU - Pedersen, Oluf

AU - Sørensen, Thorkild I.A.

PY - 2010/1

Y1 - 2010/1

N2 - 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 (n753, BMI31.0 kg m 2) and a randomly selected group (n874) 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 OR1.06-1.14 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 OR1.03-1.15 per z-score units), and peripheral fatness (OR1.15-1.20 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 OR0.64-0.84 per mol l 1), significantly at S-46. The rs17700633 A-allele was significantly associated with insulin (OR1.25 per 50 pmol l 1), leptin (OR1.42 per 10 ng l 1) and insulin sensitivity (OR0.81 per model unit). The rs17782313 C-allele and the rs17700633 A-allele were both associated with BMI in childhood and adolescence (range of OR1.04-1.17 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.

AB - 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 (n753, BMI31.0 kg m 2) and a randomly selected group (n874) 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 OR1.06-1.14 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 OR1.03-1.15 per z-score units), and peripheral fatness (OR1.15-1.20 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 OR0.64-0.84 per mol l 1), significantly at S-46. The rs17700633 A-allele was significantly associated with insulin (OR1.25 per 50 pmol l 1), leptin (OR1.42 per 10 ng l 1) and insulin sensitivity (OR0.81 per model unit). The rs17782313 C-allele and the rs17700633 A-allele were both associated with BMI in childhood and adolescence (range of OR1.04-1.17 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.

U2 - 10.1038/ijo.2009.215

DO - 10.1038/ijo.2009.215

M3 - Journal article

C2 - 19844209

SN - 0307-0565

VL - 34

SP - 182

EP - 189

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 1

ER -