The association between dietary quality indices, serum concentrations of alpha-MSH and AgRP and Melanocortin-4 receptor (MC4R) gene polymorphisms and their signatures in obese adults

Abstract

Background and aims: Obesity is a multi-factorial metabolic disturbance which is believed to be determined by genetic and environmental factors and their complex interactions. Variations in melanocortin 4 receptor (MC4R) are known as the second association signal for common obesity. However, the results of previous studies regarding this association are inconclusive. This observed inconsistency might be due to the role of lifestyle factors specially diet in modulation of the effects of MC4R gene variation. Therefore, the purpose of the current study was to examine potential interactions between diet quality indices and polymorphisms of MC4R gene and their signatures and also evaluate the association of these variations and diet quality indices with plasma α-melanocyte stimulating hormone (α-MSH) and Agouti related protein (AgRP) concentrations among obese adults. Methods: This descriptive analytical study recruited 188 (96 males and 92 females) healthy obese adults aged 20-50 years. Diet quality indices including Healthy Eating Index-2015 (HEI-2015), Diet Quality Index-International (DQI-I), Dietary Approach to Stop Hypertension (DASH) score and Mediterranean Dietary Score (MDS) were calculated using a validated 132-item Food Frequency Questionnaire (FFQ). Polymorphisms were genotyped by HRM-PCR and PCR-RFLP. Anthropometric and biochemical characteristics and blood pressure were measured in all subjects. Data were analyzed by Kruskal-Wallis, Chi-square, ANOVA and ANCOVA tests. Results: The frequency of minor allele of rs2229616, rs52820871 and rs17782313 polymorphisms were 3.1%, 1% and 37% respectively. Adherence to the HEI modified the effects of MC4R rs17782313 polymorphisms on levels of Low-density lipoprotein-cholesterol (LDL-C) in women (P Interaction= 0.04). Among female group, rare allele heterozygotes of rs17782313 had highest mean of LDL-C concentration when placed in second tertile of HEI. Furthermore, in male group, gene-diet interactions were detected between both HEI and DQI-I and MC4R rs17782313 on glucose level and also the gene-DQI-I interactions were found in relation to systolic blood pressure (SBP) and diastolic blood pressure (DBP) and these interactions remained significant even after adjustment for potential confounders (P Interaction< 0.05). The risk allele was associated with higher SBP, DBP and serum glucose level, when the adherence to this index was lowest. On the other hand, the significant interactions were found between adherence to DASH score and MC4R rs17782313 genotypes on SBP, atherogenic index of plasma (PInteraction= 0.045), serum glucose (PInteraction= 0.021) and triglyceride (PInteraction= 0.020) concentrations and plasma AgRP level (PInteraction= 0.050) among females. Among males, after adjustment for confounding variables, significant interactions were revealed between MC4R re17782313 and DASH and MDS on glucose (PInteraction= 0.037) and α–MSH (PInteraction= 0.050) levels, respectively. Such that the male carriers of the risk allele with the lowest adherence to these indices (MDS and DASH) had higher α–MSH and glucose concenterations. After adjustment for confounders, a similar interaction was observed between DASH and MC4R rs17782313 in relation to plasma level of AgRP among women. Moreover, a significant association was found between rs17782313 and AgRP levels among men; minor homozygote carriers of rs17782313 had lower adjusted means of AgRP levels compared with other genotypes. Conclusions: The present study showed that adhearence to dietary quality indices (HEI-2015, DQI-I, MDS and DASH score) may interacts with MC4R gene polymorphism (rs17782313) ) to influence cardio-metabolic risk factors. These interactions were more considerabley observed in subjects who were geneticaly susceptible to obesity. replication in prospective cohort studies among different populations is recommended to confirm this finding and also molecular studies are requiered to recognize exact mechanisms behind these observed interactions.