An Association between Diet and MC4R Genetic Polymorphism, in Relation to Obesity and Metabolic Parameters—A Cross Sectional Population-Based Study

Abstract

The melanocortin-4 receptor (MC4R) gene harbours one of the strongest susceptibility loci for obesity and obesity-related metabolic consequences. We analysed whether dietary factors may attenuate the associations between MC4R genotypes and obesity and metabolic parameters. In 819 participants genotyped for common MC4R polymorphisms (rs17782313, rs12970134, rs633265, and rs135034), the anthropometric measurements, body fat content and distribution (visceral and subcutaneous adipose tissue, VAT and SAT, respectively), and blood glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides concentrations, and daily macronutrient intake were assessed. ANOVA or Kruskal–Wallis tests were used, and multivariate linear regression models were developed. We observed that the CC genotype carriers (rs17782313) presented higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations when they were stratified to the upper quantiles of protein intake. An increase in energy derived from proteins was associated with higher BMI (Est. 5.74, R2 = 0.12), body fat content (Est. 8.44, R2 = 0.82), VAT (Est. 32.59, R2 = 0.06), and VAT/SAT ratio (Est. 0.96, R2 = 0.05). The AA genotype carriers (rs12970134) presented higher BMI, body fat, SAT and VAT, fasting blood glucose, triglycerides and total cholesterol concentrations. An increase in energy derived from proteins by AA carriers was associated with higher VAT (Est.19.95, R2 = 0.06) and VAT/SAT ratio (Est. 0.64, R2 = 0.05). Our findings suggest that associations of the common MC4R SNPs with obesity and its metabolic complications may be dependent on the daily dietary intake, which may open new areas for developing personalised diets for preventing and treating obesity and obesity-related comorbidities.

Gene–Environment Interaction on Type 2 Diabetes Risk among Chinese Adults Born in Early 1960s

“…Additionally, the impact of T2D differs by population, depending on some variables (e.g., age, race, ethnicity, geography, and socioeconomic status) [11]. Previous studies have found that some environmental factors may regulate the expression of genes and influence susceptibility of T2D, such as gene-diet interaction, in smokers and alcohol drinkers [11][12][13][14][15][16][17]. Few studies have examined the interacitons of other environmental factors with single nucleotide polymorphisms (SNPs) on T2D risk in the Chinese population.…”

Association of the rs17782313, rs17773430 and rs34114122 Polymorphisms of/near MC4R Gene with Obesity-Related Biomarkers in a Spanish Pediatric Cohort

“…Moreover, MC4R activation has been shown to result in decreased food intake and increased energy expenditure. Single nucleotide polymorphisms (SNPs) mapped to this gene have been identified as predisposing carriers to obesity and related comorbidities [11,12]. The SNP rs17782313 has been shown multiple times to be associated with obesity [13][14][15][16] and with insulin resistance, dyslipidemia and type 2 diabetes risk [16][17][18][19][20].…”

Immune Response and Lipid Metabolism Gene Polymorphisms Are Associated with the Risk of Obesity in Middle-Aged and Elderly Patients

“…Genome-wide association studies (GWAS) allow identifying genetic variants associated with susceptibility to overweight and obesity [7]. In adults, the strongest associations with the risk of obesity were discovered for single-nucleotide polymorphisms (SNPs) in the FTO, MC4R, TMEM18, TNNI3K, SEC16B, GNPDA2, POMC, RPGRIP1L, IRX3, and IRX5 genes [8][9][10][11]. Moreover, it was shown that the genetic susceptibility to obesity is modified in a population-related manner [12][13][14].…”