J Korean Diabetes Assoc.  2003 Apr;27(2):123-131.

Polymorphism of Melanocortin-4 Receptor and Obesity

• Kim HS
• Lee IK
• Suh YS

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.

Keyword

Melanocortin-4 receptor; Obesity; Metabolic syndrome

MeSH Terms

Adipose Tissue
Anthropometry
Blood Glucose
Body Weight
Codon
Eating
Energy Metabolism
Fasting
Female
Genetics
Genotype
Heterozygote
Homozygote
Humans
Intra-Abdominal Fat
Isoleucine
Male
Obesity*
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Prevalence
Receptor, Melanocortin, Type 4*
Valine
Waist-Hip Ratio
Codon
Isoleucine
Receptor, Melanocortin, Type 4
Valine