Negative Association of MC3R Variants with Weight and Blood Pressure in Cape Town Pupils Aged 11-16 Years (Original Articles) (Melanocortin 4 Receptor Gene) (Report‪)‬

Obesity is a multifactorial body weight abnormality resulting from genetic and environmental interactions. Of the body mass index (BMI) variation among obese individuals of different populations and within the same family, 40-70% are estimated to be inherited, and 30% are attributed to cultural and socio-economic factors. (1,2) More than 100 genes have been implicated in the heterogeneity of body weight, among which are genes that encode proteins or peptides of the central nervous system that affect conscious and unconscious aspects of energy intake and expenditure. Melanocortin receptors, particularly the melanocortin 4 receptor gene (MC4R), play a major role in the development of both monogenic and polygenic obesity. (3,4) Mutations in MC4R are the most common cause of early onset obesity, accounting for up to 6%, particularly in white populations. (3) Furthermore, more than 50 additional MC4R single nucleotide polymorphisms have been reported in obese and control individuals, with different effects depending on the population and family studied. (4) Recently, obesity-related mutations (A293T, I335S, X361S, I183, A70T and M134I) have been identified in the melanocortin-3 receptor gene (MC3R) - another energy-regulating melanocortin receptor. (5,6) Similar to MC4R polymorphisms, common variants in MC3R show significant frequency variation among different populations, accompanied by controversial effects on obesity phenotypes. (5,7) Epidemiological studies8 show that overweight and obesity prevalence rates in South African pupils are fast approaching those observed in developed countries, but the contribution of genetic factors is under-investigated. We analysed MC4R and MC3R for sequence variants that may contribute to the development of obesity in pupils from South Africa.