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

Abstract

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/m(2) 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.

Figure 1.

The geometric means (± standard errors) of BMI (at 1986) by the genotypes of SNP rs17782313 in different age groups among women, <45, 45–49.5, 50–54.9, 55–59.5, 60–64.9, 65–69.9 and ≥70 years old. The analyses were adjusted for diabetes status. *P < 0.05.

Figure 2.

The geometric means (standard errors) of BMI (at 1986) of carriers and non-carriers of the risk allele-C of MC4R SNP rs17782313 by height (<160, 160–149 and ≥165 cm). The analyses were adjusted for age and diabetes status. P for interaction between the genotype and height is 0.04.

Figure 3.

Odds ratios (P-values) of type 2 diabetes associated with rs17782313 genotypes. Multivariable analysis adjusted for age, BMI, waist circumference, smoking, alcohol consumption, physical activity and menopausal status. Error bars denote 95 percent confidence intervals.