MC4R Single Nucleotide Polymorphisms Were Associated with Metabolically Healthy and Unhealthy Obesity in Chinese Northern Han Populations.

Luying Gao,Hui Pan,Hongbo Yang,Linjie Wang,Huijuan Zhu,Fengying Gong

doi:10.1155/2019/4328909

Abstract

Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients. Therefore, we aimed to study single nucleotide polymorphisms (SNPs) in the MC4R gene associated with metabolically healthy and unhealthy obesity in Chinese Northern Han populations. A total of 1100 Chinese Northern Han subjects were recruited and divided into four groups according to the criteria of the Adult Treatment Panel-III (ATP-III) and World Health Organization (WHO): MUHO (n = 300), MHO (n = 196), metabolic unhealthy normal weight (MUH-NW) (n = 303), and metabolic healthy normal weight (MH-NW) (n = 301). DNA samples were extracted, and six SNPs of the MC4R gene, including rs2331841, rs656710, rs17782313, rs571312, rs12970134, and rs11872992, were genotyped with the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. Among the six SNPs of the MC4R gene, rs2331841 (A/G) was the most significant and could account for 0.9% of obesity etiology. Compared with the normal weight group, rs2331841 of the MC4R gene was associated with obesity (P=0.032). The obesity risk of subjects with the AG genotype in the rs2331841 site was 82% higher than the risk of those with the GG genotype (β = 0.60, OR = 1.82, P=0.030). After adjusting for sex and age, the frequency of the A allele in the rs2331841 site was higher in the MUHO group than in the MH-NW group (27.9% vs. 21.1%, respectively, OR = 1.49, 95% CI 1.14–1.96, P=0.005) and in the MUHO group than in the MHO group (27.9% vs. 22.3%, respectively, OR = 1.39, 95% CI 1.02–1.92, P=0.039). Among the three genotypes of rs2331841, the subjects with the AA/AG genotype had higher diastolic blood pressure (DBP) than those with the GG genotype. Our data first suggest that SNPs in the rs2331841 site of the MC4R gene are closely related to obesity and its related metabolic disorders in Chinese Northern Han populations. The participants with an A allele of rs2331841 had a higher risk of obesity and MUHO than other participants.

Highlights

Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients
Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity by the Genome-Wide Association Study (GWAS) [5]. e single nucleotide polymorphisms (SNPs) at rs12970134, rs17782313, rs571312, rs2331841, rs6567160, and rs11872992 in/near the melanocortin-4 receptor (MC4R) gene have been associated with lower energy expenditure in overweight and obese children and adults [6,7,8,9]
Obesity was defined as body mass index (BMI) ≥30 kg/m2, and BMI ≤25 kg/m2 was considered normal weight based on the criteria of the World Health Organization (WHO). e obesity group and normal weight group were subdivided into metabolically healthy and metabolically unhealthy subgroups based on the criteria of the Adult Treatment Panel-III (ATP-III) (high triglycerides (≥1.7 mmol/L), elevated SBP (≥130 mmHg) or diastolic blood pressure (DBP) (≥85 mmHg), higher FBP (≥5.6 mmol/L), and lower HDL-cholesterol (1.04 mmol/L for men and 1.29 mmol/L for women))