Human Molecular Genetics Advance Access originally published online on August 12, 2008
Human Molecular Genetics 2008 17(22):3502-3508; doi:10.1093/hmg/ddn242
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The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women
1 Department of Nutrition 2 Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA 3 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed at: Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. Tel: +1 6174324116; Fax: +1 6174322435; Email: nhlqi{at}channing.harvard.edu or luqi{at}hsph.harvard.edu
Received July 1, 2008; Accepted August 11, 2008
Melanocortin-4 receptor (MC4R) plays critical roles in regulating food intake and energy balance. Recent genome wide scans found common variants near MC4R were related to obesity and insulin resistance. We examined the associations of the reported variants rs17782313 (T>C) and rs17700633 (G>A) with dietary intakes, weight change and diabetes risk in 5724 women (1533 with type 2 diabetes) from a prospective cohort. Under an additive inheritance model, SNP rs17782313 was significantly associated with high intakes of total energy (P = 0.028), total fat (P = 0.008) and protein (P = 0.003). Adjustment for age, BMI, diabetes status and other covariates did not appreciably change the associations. The SNP was also associated with significantly increasing trend of percentage of energy from total fat (P for trend = 0.037). The associations between SNP rs17782313 and higher BMI (P = 0.002) were independent of dietary intakes. In addition, carriers of allele-C had 0.2 kg/m2 greater 10-year increase in BMI from cohort baseline 1976 to 1986 (P = 0.028) compared with the non-carriers. Moreover, per allele-C of rs17782313 was associated with 14% (2–32%) increased risk of type 2 diabetes, adjusting for BMI and other covariates. SNP rs1770833 was not significantly associated with either dietary intakes or obesity traits. In conclusion, the common SNP rs17782313 near MC4R gene was significantly associated with higher intakes of total energy and dietary fat. In addition, the SNP was related to greater long-term weight change and increased risk of diabetes in women.
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