Negative association of MC3R variants with weight and blood pressure in Cape Town pupils aged 11 - 16 years.

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.