Background: Human and animal studies support the role of MC4R and MC3R in human obesity, but limited data are available on the genetic contribution to obesity in South African populations.
Objective: To screen obese-overweight South African pupils for MC3R and MC4R polymorphisms that may play a role in the development of obesity.
Design: A cross-sectional study screened 227 obese-overweight (115 black and 112 coloured) and 204 normal weight (94 black, 110 coloured) school pupils for the presence of MC4R and MC3R polymorphisms using a single strand conformation polymorphism, subsequent sequencing, and allele specific restriction enzyme analysis.
Results: Two polymorphisms were detected in the MC3R (T6K and V81I) but none in MC4R. After adjusting for age, gender and case-control status, the frequency distributions of T6K and V81I genotype and allele varied significantly between the ethnic groups. The frequency of the V81I A allele was significantly lower in coloured overweight-obesity than normal pupils. In coloured pupils, both polymorphisms were associated with obesity indices and total cholesterol. The T6K A allele was also associated with lower blood pressure. Likewise, different T6K-V81I haplotypes demonstrated negative associations with obesity indices and blood pressure.
Conclusion: We demonstrated that the MC3R polymorphisms have a protective effect on metabolic traits; however, further analysis is required to confirm whether this translates to a lower incidence of metabolic syndrome in coloured populations.