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J Korean Diabetes Assoc. 2003 Apr;27(2):123-131. Korean. Original Article.
Kim HS , Lee IK , Suh YS .
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
Department of Family Medicine, Keimyung University School of Medicine, Daegu, Korea.
Abstract

BACKGROUND: The application of genetics to obesity has made remarkable progress in recent years. The melanocortin-4 receptor (MC4R) regulates food intake, and possibly that of energy expenditure. The MC4R gene is the most prevalent obesity gene found to date in humans. The prevalence of single nucleotide substitution, replacing valine with isoleucine, at codon 103 was studied, and the role of the MC4R gene polymorphism on the body weight, fat distribution and lipid profile were determined. METHODS: Anthropometry and biochemical studies were performed on 226 subjects (82 male and 144 female subjects). The MC4R genotype was determined by a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. The body fat distributions were measured by computerized tomography. RESULTS: The frequencies of the homozygotes, Val103Val and Val103/Ile, were 88.9 and 11.1%, respectively. The frequencies of the heterozygotes were similar (11.8 vs. 10.6%) in the control and obese groups. However, the heterozygotes had lower waist-to-hip ratios (WHR) (p=0.033) and visceral fat masses (p=0.038) compared to the homozygotes. In the obese group, the heterozygotes had lower body mass indices (BMI) and visceral fat masses (p=0.043 and p=0.044, respectively). The heterozygote males had lower BMI and fasting plasma glucose levels (p=0.046 and p<0.001, respectively) than the homozygote males. The heterozygote females tended to have lower WHR (p=0.081) than the homozygote females. CONCLUSION: These results suggest that mutations in the MC4R gene are likely to be a cause of human obesity, and possibly of metabolic syndrome.

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