Abstract
BackgroundThe melanocortin-4 receptor (MC4R) regulates metabolism by modulating eating behavior and MC4R variants (rs17782313 and rs571312) are associated with obesity in Asians and Caucasians. However, the impact of their interactions with nutritional and lifestyle factors on obesity are poorly described. Therefore, we investigated the interaction of MC4R variants and dietary patterns on the risk of obesity in Korean middle-aged adults.MethodsData collected included, genetic variations, anthropometric and biochemical measurements, dietary and lifestyle habits, and food intake. Data were obtained from the 8830 adults aged 40–69 years in the Ansung and Ansan cohort of the Korean Genome Epidemiology Study.ResultsThe MC4R rs18882313 minor allele had a higher frequency in the obese group (P < 0.01). MC4R genotypes were not associated with differences in daily energy and macronutrient intakes. However, the intakes of processed foods and fat (as percentages of energy) were significantly higher and intake of fruits were significantly lower in subjects with MC4R minor alleles (P < 0.05). Interestingly, there was a positive interaction between MC4R variants and mental stress levels that were associated with the risk of obesity after adjusting for age, gender, residence area, daily energy intake, smoking status and physical activity (interaction P = 0.0384). Only in subjects with high stress were MC4R minor alleles associated with higher BMIs after adjusting for confounders. The association was present without modulating energy and nutrient intake. In the group with energy intakes higher than estimated energy requirement (EER), subjects with MC4R minor alleles had higher BMIs than those with the major alleles (P < 0.001).ConclusionsThe interactions of mental stress and energy intakes with the MC4R minor allele genotype might be associated with increased risk of obesity in Korean adults. This research might identify subjects with a specific MC4R minor alleles as a human subset of people with a low metabolic tolerance for excessive energy intake, especially when under stress.
Highlights
The melanocortin-4 receptor (MC4R) regulates metabolism by modulating eating behavior and MC4R variants are associated with obesity in Asians and Caucasians
In Korea, the MC4R variant rs17782313 was associated with body mass index (BMI) in a replication gene association study and a Genome-wide association studies (GWAS) [16, 17] and BMI increased with C allele of MC4R rs17782313 by 0.22 kg/m2 BMI [17]
Drinking was associated with higher rates of overweight and obesity but smoking was associated with lower rates of obesity (Table 1)
Summary
The melanocortin-4 receptor (MC4R) regulates metabolism by modulating eating behavior and MC4R variants (rs17782313 and rs571312) are associated with obesity in Asians and Caucasians. Other genes associated with obesity have since been reported, including the melanocortin-4 receptor (MC4R) [5], adiponectin, C1Q and collagen domain containing [6], brain-derived neurotrophic factor [7], leptin [8], peroxisome proliferator-activated receptor gamma-2 [9] and SH2B1 genes [10] Among these genes, some single-nucleotide polymorphisms (SNPs) near MC4R (rs17782313, rs571312, rs17700144, and rs2331841) are strongly associated with obesity in adults, adolescents, and children, indicating that subjects with minor alleles of these SNPs typically exhibit higher BMIs than those with the major allele [3, 11,12,13]. Subjects with the minor allele of MC4R rs17782313 exhibited a positive association with BMI and it tended to be related to a positive energy balance with possible impacts on dietary intake [18]
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