The association between downstream of MC4R gene polymorphism with insulin resistance and appetite in obese adults

Abstract

Background and aims: obesity is known as a chronic disease and an important risk factor for several major non-communicable diseases. Obesity is a multi-factorial disorder arising from interaction between numerous factors including life style (particularly diet and physical activity) and genetics. The leptin-melanocortin system plays an important role in the regulation of food storage and energy homeostasis. Variations in melanocortin 4 receptor (MC4R) are known as the second association signal for common obesity. Evidence shows that rs17782313 polymorphisms in down-sterim MC4R gene is associated with increased risk of obesity and insulin resistance in Asians adult. However, the results of previous studies regarding this association are inconsistent. Therefore, the purpose of the current study was to examine the association between downstream of MC4R gene polymorphisms with resistance insulin and appetite among obese adults. Method and materials: In the current cross-sectional study, 180 obese adults, aged between 20 to 50 years old were enrolled. Participants were apparently healthy volunteers that were invited by invitation letters or posters. Obesity was defined as BMI between 30 - 40 kg / m2. Dietary intake were calculated from a validated 132-item Food Frequency Questionnaire (FFQ). Anthropometric characteristics [wieght, body mass index (BMI), waist circumference (WC), hip circumference (HP), waist to hip ratio (WHR)], physical activity, [fasting blood sugar (FBS), insulin, homeostasis model of assessment-estimated insulin resistance (HOMA-IR)], blood pressure [Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)], were measured in all subjects. Visual Analogue Scale (VAS) was used for appetite assessments. Polymorphism was genotyped by PCR-RFLP. Data were analyzed by ANOVA, Chi-square and Kruskal wallis tests. Results: The total of 180 subjects 90 (54.8%) were homozygotes for the rs17782313 polymorphism and 81 (36.2 %) were heterozygotes. The frequency of minor allele was 37%. The risk allele was associated with higher serum glucose and insulin resistance, in males group. also among females, allele C (TC genotype), was assosiated with increased of hunger (P < 0.05.) There was a significant interaction between polymorphism rs17782313 MC4R gene and dietary intake on serum glucose, WC and DBP after adjustment for confounding variables. Individuals with TT genotype at the highest tertile of carbohydrate intake had the lowest WC (PInteraction = 0.047) while individual with rare allele heterozygotes of rs17782313 at the higher fat tertile dietary had the highest DBP (PInteraction = 0.035). Also, homozygotes individuals for high-risk alleles (CC genotypes) had the highest serum glucose at higher tertile of protein intake (PInteraction = 0.001). Conclusions: rs17782313 Polysomorphism appears to be associated with increased appetite, serum glucose and insulin resistance in obese adults. Dietary intake of macronutrients can also moderate the association of this polymorphism with some biochemical and anthropometerics parameters.