Abstract. Objective: The genetic variants near the melanocortin-4 receptor gene (MC4R), a key protein regulating energy balance and adiposity, have been related to obesity and cardiovascular risk factors. However, qualitative and quantitative aspects of diet may modulate the association of this polymorphism with obesity and cardiovascular diseases (CVDs). The aim of this study was to evaluate interactions among MC4R rs17782313, the Dietary Approaches to Stop Hypertension (DASH) diet and risk factors for CVDs. Method: This cross-sectional study was conducted on 266 Iranian women categorized by body mass index (BMI) range of 25–40 kg/m2 as overweight or obese. CVD risk factors included waist circumference (WC), lipid profile, blood pressure, insulin circulation and fasting blood sugar (FBS). Insulin and FBS were used to calculate homeostatic model assessment insulin resistance (HOMA-IR) Body composition was assessed by a multi-frequency bioelectrical impedance analyzer, InBody 770 scanner. Results: The findings of this study show that high adherence to the DASH diet in the CC groups were associated with decreased SBP and DBP compared to the TT group. In addition, a significant difference between women with high adherence to the DASH diet compared to low adherence was observed for body weight (p < 0.001), fat free mass (FFM) (p = 0.01) and BMI (p = 0.02). Women with the CC genotype had higher insulin (mg/dl) (mean and SD, for TT: 14.6 ± 4.6, TC: 17.3 ± 9.2, CC: 15.3 ± 4.8, p = 0.04) and HOMA-IR (mean for and SD, TT: 3.1 ± 1.07, TC: 3.9 ± 2.4, CC: 3.2 ± 1.1, p = 0.01) than TT group. Inclusion of potential confounding variables (age, physical activity, BMI and daily caloric intake) did not attenuate the difference. Conclusion: Among overweight/obese Iranian women with the CC genotype, incorporating the DASH diet may serve as a dietary prescription to decrease CVD risk. A dietary intervention trial is warranted.
