Dietary Behaviours May Modulate the Association Between Common MC4R Genetic Variants and Obesity and Its Comorbidities: The 1000PLUS Cohort Study.

Abstract

Background: The MC4R gene harbours one of the strongest susceptibility locus for obesity, and its metabolic consequences. The objective of this study was to analyze whether dietary factors may attenuate the MC4R genotypes effects on obesity and its comorbidities.Methods: In 819 adult participants, genotyped for MC4R SNPs (rs17782313, rs12970134, rs633265, rs1350341) the anthropometric measurements, total body fat, visceral (VAT) and subcutaneous adipose tissue (SAT), blood glucose, insulin, total-, LDL-, HDL-cholesterol, and triglycerides concentrations were assessed. The daily macronutrient intake was calculated based on the three-day food intake records, and daily physical activity based on the validated questionnaire. The ANOVA or Kruskal-Wallis tests were used, and multivariate linear regression models were developed to evaluate the effects of diet on obesity and related factors in various genotypes carriers.Results: The CC genotype (rs17782313) carriers, being in the upper quantiles of protein intake, presented significantly higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations, and an increase of energy derived from proteins was associated with significantly higher BMI (Est. 5.74, R2=0.12), body fat content (Est. 8.44, R2=0.82), VAT (32.59, R2=0.06), and VAT/SAT ratio (Est. 0.96, R2=0.05). The AA genotype carriers (rs12970134) being in the upper protein intake quantiles presented higher BMI, body fat, SAT and VAT volume, waist circumference, fasting blood glucose, triglycerides and total cholesterol concentrations. Individuals carrying the AG and GG genotypes in the upper carbohydrate intake quantile had significantly lower body weight, waist circumference, insulin resistance and fasting insulin levels. An increase of energy derived from proteins by AA carriers was associated with significantly higher VAT (Est. 19.95, R2=0.06) and VAT/SAT ratio (Est. 0.64, R2=0.05).Conclusions: Our findings provide evidence that associations of the common MC4R SNPs with obesity and its comorbidities is modulated by dietary intake, and may be useful for genome-customized diets for obesity prevention.Trial registration. This trial was registered at www.clinicaltrials.gov as NCT03792685. Date of registration: 3Jan2019 (retrospectively registered), https://clinicaltrials.gov/ct2/show/NCT03792685.