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Review Article

A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism

Kimia Mohammadhasani1,*orcid, Mohammad Vahedi Fard1,*orcid, Mehran Yadegari1orcid, Mehdi Barati2orcid, Hossein Bahari3orcid, Elyas Nattagh-Eshtivani1orcid, Mohammad Rashidmayvan1orcid
Clinical Nutrition Research 2024;13(3):214-225.
Published online: July 26, 2024

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Correspondence to Elyas Nattagh-Eshtivani. Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Science, Gonabad 9597118949, Iran. Nattagh.elyas@gmail.com
Correspondence to Mohammad Rashidmayvan. Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Science, Gonabad 9597118949, Iran. Rashidmayvan@gmail.com

*Kimia Mohammadhasani and Mohammad Vahedi Fard equally contributed as first authors.

• Received: May 8, 2024   • Revised: July 19, 2024   • Accepted: July 23, 2024

Copyright © 2024. The Korean Society of Clinical Nutrition

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A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism
Clin Nutr Res. 2024;13(3):214-225.   Published online July 26, 2024
DOI: https://doi.org/10.7762/cnr.2024.13.3.214
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A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism
Clin Nutr Res. 2024;13(3):214-225.   Published online July 26, 2024
DOI: https://doi.org/10.7762/cnr.2024.13.3.214
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A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism
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Figure 1 α-MSH and AgRP control food consumption and energy intake by stimulation and inhibition of the melanocortin 4 receptor. MC4R is stimulated by α-MSH, which reduces appetite and food intake. In contrast, AgRP inhibits MC4R and increases food intake. Leptin secreted by adipocytes that decreases food intake by acting on anorectic POMC neurons and stimulating α-MSH in the hypothalamus. Insulin secreted by beta cells in the pancreas and stimulates α-MSH secretion through a pathway similar to leptin. In contrast, Ghrelin sends signals to AgRP neurons and stimulates the secretion of AgRP. Ghrelin is released during hunger from the gastrointestinal tract and increases appetite.AgRP, agouti-related protein; α-MSH, α-melanocyte stimulating hormone; ACTH, adrenocorticotropic hormone MC4R, melanocortin 4 receptor; NF, nuclear factor; POMC, pro-opiomelanocortin.

Figure 1

A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism
Negative↓Basal metabolic rate and high-density lipoprotein cholesterol↑Low-density lipoprotein cholesterolAlizadeh et al. [14] (2022)Interaction of MC4R rs17782313 Variants and Dietary Carbohydrate Quantity and Quality on Basal Metabolic Rate and General and Central Obesity in Overweight/Obese Women: A Cross-Sectional StudyCross-sectionalrs17782313 (CC & TC)282 females, healthy18–56 ≥ 25 kg/m2 Negative↑Waist circumference and body mass indexAdamska-Patruno et al. [15] (2021)An Association Between Diet and MC4R Genetic Polymorphism, in Relation to Obesity and Metabolic Parameters-A Cross Sectional Population-Based StudyCross-sectionalrs17782313 (CC)1,549, males and females, type 2 diabetes18–79 > 25 kg/m2 Negative↓Subcutaneous fat content (SAT)↑Body mass index, body fat content, visceral fat content (VAT), and VAT/SAT ratiosMohammadi et al. [16] (2020)The Interaction Between Dietary Non-Enzymatic Antioxidant Capacity (NEAC) With Variants of Melanocortin-4 Receptor (MC4R) 18q21.23-rs17782313 Locus on Hypothalamic Hormones and Cardio-Metabolic Risk Factors in Obese Individuals From IranCross-sectionalrs17782313 (CC)287 males and females, healthy20–50 ≥ 30 kg/m2 Positive & negative↓High-density lipoprotein cholesterol, quantitative insulin sensitivity check index, insulin, serum glucose, α-melanocyte stimulating hormone, and triglycerideElhamKia et al. [17] (2022)The Interaction Between Dietary Total Antioxidant Capacity and MC4R Gene and HOMA-IR in Metabolically Healthy and Unhealthy Overweight and Obese WomenCross-sectionalrs17782313 (CC & TC)237 females, healthy18–50, 25–40 kg/m2 Not significantNo significant associations were found with lipid profile and metabolic parameters.Khodarahmi et al. [18] (2020)Dietary Quality Indices Modifies the Effects of Melanocortin-4 Receptor (MC4R) rs17782313 Polymorphism on Cardiometabolic Risk Factors and Hypothalamic Hormones in Obese AdultsCross-sectionalrs17782313 (CC & TC)188 males and females, healthy20–50 ≥ 30 kg/m2 Positive↓Low-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, and serum glucose levelsZarei et al. [19] (2022)The Interaction Between Alternative Healthy Eating Index and MC4R rs17782313 Gene Variants on Central and General Obesity Indices in Women: A Cross‐Sectional StudyCross-sectionalrs17782313 (CC)291 females, healthy18–48 ≥ 25 kg/m2 Positive↓Visceral fat area, fat mass, body mass index, and hip circumferenceKhodarahmi et al. [20] (2020)Melanocortin-4 Receptor (MC4R) rs17782313 Polymorphism Interacts With Dietary Approach to Stop Hypertension (DASH) and Mediterranean Dietary Score (MDS) to Affect Hypothalamic Hormones and Cardio-Metabolic risk Factors Among Obese IndividualsCross-sectionalrs17782313 (CC)288 males and females, healthy20–50 ≥ 30 kg/m2 Positive↓Systolic blood pressure, atherogenic index of plasma, serum glucose, and triglyceride levelsOrtega-Azorín et al. [21] (2012)Associations of the FTO rs9939609 and the MC4R rs17782313 Polymorphisms With Type 2 Diabetes Are Modulated by Diet, Being Higher When Adherence to the Mediterranean Diet Pattern Is LowCase-controlrs17782313 (CC)7,052, male and female mean BMI 29.9 kg/m2 Mean age 70, type 2 diabetesPositiveThe MC4R rs17782313 interacted with the Mediterranean diet in its relation to type 2 diabetes.Koochakpoor et al. [22] (2016)Effect of Interactions of Polymorphisms in the Melanocortin‐4 Receptor Gene With Dietary Factors on the Risk of Obesity and Type 2 DiabetesSystematic reviewrs17782313 (CC)Not clear, male and femaleNot clear, type 2 diabetesPositiveMediterranean diet interacted with MC4R rs17782313 on the risk of type 2 diabetes.Rasaei et al. [23] (2023)Investigation the Interaction of Dietary Fat Quality Indices and the MC4R Gene in Metabolically Healthy and Unhealthy Overweight and Obese WomenCross-sectionalrs17782313 (CC)279 females, healthy18–68, 25–40 kg/m2 Negative↑Homeostatic model assessment for insulin resistance indexAoun et al. [24] (2022)The Interaction Between Genetic Polymorphisms in FTO, MC4R and MTHFR Genes and Adherence to the Mediterranean Diet in Relation to ObesityCross-sectionalrs17782313 (CC & TC)392 males and females, healthyNot clearNo significantNo significant association with waist circumference, waist-hip ratio, and body mass indexMohammadi et al. [25] (2020)Dietary Patterns Interact With the Variations of 18q21. 23 rs17782313 Locus on the Regulation of Hypothalamic-Pituitary Axis Hormones and Cardio-Metabolic Risk Factors in ObesityCross-sectionalrs17782313 (CC)288 males and females, healthy20–50 ≥ 30 kg/m2 Negative↑Systolic blood pressure and agouti-related protein levelsHosseininasab et al. [9] (2022)Are There Any Interactions Between Modified Nordic-Style Diet Score and MC4R Polymorphism on Cardiovascular Risk Factors Among Overweight and Obese Women?Cross-sectionalrs17782313 (CC & TC)282 females, healthy18–48 ≥ 25 kg/m2 Positive↓Visceral fat level, total cholesterol, and low-density lipoprotein cholesterol levelsYarizadeh et al. [10] (2021)The Interaction Between the Dietary Inflammatory Index and MC4R Gene Variants on Cardiovascular Risk FactorsCross-sectionalrs17782313 (CC)266 females, healthy18–56, 25–45 kg/m2 Positive↑Higher high-density lipoprotein cholesterol levels↓Low-density lipoprotein cholesterol and triglyceride levelsYarizadeh et al. [26] (2020)The Interaction Between Dietary Approaches to Stop Hypertension and MC4R Gene Variant in Predicting Cardiovascular Risk FactorsCross-sectionalrs17782313 (CC)266 females, healthy18–50, 25–40 kg/m2 Positive↓Systolic blood pressure and diastolic blood pressure
Table 1 A review of studies that examined the effect of interaction between MC4R rs17782313 and diets.

Table 1

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