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.University Research Fund of the Cape Peninsula University of Technology, Harry Crossley and the National Health Laboratory Services

Association of cocaine- and amphetamine- related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African

Background/Aims: Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Methods: Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. Results: The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys109Arg G allele was associated with an average reduction of 2.36 kg/m2 in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Conclusion: Our findings suggest that c.517A→G and Lys109Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group

Association of the ENPP1 rs997509 polymorphism with obesity in South African mixed ancestry learners

Background: The Ectonucleotide Pyrophosphatase Phosphodiesterase1 (ENPP1) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other components of the metabolic syndrome. Design: A case-control study. Subjects: Sixty four obese and 64 lean mixed ancestry learners. Setting: Western Cape, South Africa. Main outcome measure: The ENPP1 rs997509T allele is independently associated with obesity in children of mixed ancestry from South Africa. Results: The T allele frequency of the rs997509 differed significantly between obese and controls, p=0.0100 and increased the risk of being obese, p = 0.0238. Furthermore, the estimated effect of the T allele was an increase of 8.6 cm in waist circumference, 10.2 kg in weight and a corresponding 4.9 kg/m2 in BMI. Individuals carrying both the 121Q and the T allele of rs997509 were more associated with obesity (odds ratio = 3.85, 95% CI: 1.13 to 13.09) whilst those carrying the C allele of rs997509 in the presence of 121Q were likely to be lean with odds ratio of obesity 0.41 (95% CI: 0.19 to 0.87). Conclusion: Our findings suggest that ENPP1 polymorphisms may contribute to different metabolic characteristics, all of which are associated with insulin resistance in mixed ancestry children of South Africa. However, a larger study is required to confirm findings of this study