Genetic association studies of obesity in Africa: a systematic review.

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.

Rare mutations of peroxisome proliferator-activated receptor gamma: frequencies and relationship with insulin resistance and diabetes risk in the mixed ancestry population from South Africa.

Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR), ß-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (P = 0.215). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31-0.95)). Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes.

Three-year's changes in glucose tolerance status in the Bellville South cohort: rates and phenotypes associated with progression.

AIMS: To determine the phenotypes associated with progression to type 2 diabetes or worsening in glucose tolerance during a 3-year follow-up of a community-based cohort in Cape Town, South Africa. METHODS: A total of 198 eligible subjects (72.3% women) aged 55.2 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyltransferase, cotinine, creatinine and HbA1c. Progression in glucose tolerance status at 3-year was the composite of new-onset diabetes and any worsening in glucose tolerance status. RESULTS: The cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of metabolic syndrome (MetS). In age and sex-adjusted logistic regression analyses, MetS [odd ratio: 3.08 (95% CI: 1.34-7.10)], HbA1c [5.26 (1.94-14.24)], HDL-cholesterol [0.05 (0.01-0.33)], γ-glutamyltransferase [1.99 (1.07-3.67)], triglycerides [1.71 (1.13-2.58)] and total/HDL-cholesterol [1.45 (1.08-1.93)] were significant predictors of progression, while borderline effects were observed for baseline glucose and diastolic blood pressure. Markers of adiposity were mostly stable or improved among non-progressors during follow-up, but deteriorated significantly among progressors, resulting in significant statistical interactions. CONCLUSIONS: High rates of deterioration of glucose status over time were found in our population, with nearly one-fifth of them acquiring a glucose tolerance worse status within a very short follow-up. Our study extends to this setting the well-known utility of phenotypes of MetS single or in combination, in predicting worsening in glucose tolerance status.

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

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 Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) 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 Lys(109)Arg 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.