Common Variants Associated with Type 2 Diabetes in a Black South African Population of Setswana Descent: African Populations Diverge.

The increasing worldwide prevalence of type 2 diabetes mellitus (T2D) is a serious global health concern. Although T2D has a strong genetic etiology, limited knowledge exists about the common variants associated with it in the black South African population. This study set out to evaluate the association of previously reported common variants in other world populations with T2D susceptibility in a black South African population of Setswana descent. A case-control study design of 178 cases and 178 controls nested in the Prospective Urban Rural Epidemiology (PURE) study was conducted wherein we genotyped for 77 single nucleotide polymorphisms (SNPs). PLINK software was used to evaluate the standard genetic models of disease penetrance for the association of the common variants with impaired glucose tolerance (IGT) while adjusting for age, sex, and body mass index. Only rs1436955 significantly associated with an increase in T2D risk; three other variants, rs831571, rs8050136, and rs7542900, significantly associated with decreased risk of T2D. However, none of the four SNPs had significant associations after correcting for multiple testing (p<0.05). Although further studies are required to confirm these observations, the common variants associated with T2D risk among the Black South Africans of Setswana descent might likely be different than those in the Asian and European populations. This study supports the broader thesis that the genetic background of Africans is diverse and cannot be directly extrapolated using genetic variants from other ethnicities. Therefore there is a need to identify the population-specific variants linked with T2D in Africa.

Sex differences independent of other psycho-sociodemographic factors as a predictor of body mass index in black South African adults.

To better understand the sex differences in body mass index (BMI) observed in black South African adults in the Transition and Health during Urbanization of South Africans Study, the present study investigated whether these differences can be explained by the psycho-sociodemographic factors and/or health-related behaviours. A cross-sectional survey was undertaken among 1,842 black South African individuals from 37 study sites that represented five levels of urbanization. The behavioural factors that possibly could have an influence on the outcome of body-weight and that were explored included: diet, smoking, level of education, HIV infection, employment status, level of urbanization, intake of alcohol, physical activity, and neuroticism. The biological factors explored were age and sex. The prevalence of underweight, normal weight, and overweight among men and women was separately determined. The means of the variables were compared by performing Student's t-test for normally-distributed variables and Mann-Whitney U-test for non-normally-distributed variables. The means for the underweight and overweight groups were tested for significant differences upon comparison with normal-weight individuals stratified separately for sex. The differences in prevalence were tested using chi-square tests (p<0.05). All the variables with a large number of missing values were tested for potential bias. The association between sex and underweight or overweight was tested using the Mantel-Haenszel method of odds ratio (OR) and calculation of 95% confidence interval (CI), with statistical significance set at p<0.05 level. Logistic regression was used for controlling for confounders and for testing for effect modification. Females were more likely to be overweight/obese (crude OR=5.1; CI 3.8-6.8). The association was attenuated but remained strong and significant even after controlling for the psycho-sociodemographic confounders. In this survey, the risk for overweight/obesity was strongly related to sex and not to the psycho-sociodemographic external factors investigated. It is, thus, important to understand the molecular roots of sex- and gender-specific variability in distribution of BMI as this is central to the future development of treatment and prevention programmes against overweight/obesity.

Hypoadiponectinemia is associated with progression toward type 2 diabetes and genetic variation in the ADIPOQ gene promoter.

OBJECTIVE: Adiponectin encoded by the ADIPOQ gene modulates insulin sensitivity and glucose homeostasis. The aim of the current study was to investigate whether ADIPOQ gene variants in the promoter region predict adiponectin levels and type 2 diabetes progression. RESEARCH DESIGN AND METHODS: A total of 550 subjects with increased risk of type 2 diabetes were investigated; they underwent a 75-g oral glucose tolerance test, repeated after 3 years. Adiponectin levels were analyzed, and two ADIPOQ promoter variant single nucleotide polymorphisms, -11391G>A and -11377C>G, were genotyped. RESULTS: Tertiles of the adjusted adiponectin levels were associated with single nucleotide polymorphism -11391G>A and -11377C>G haplotypes (P < 0.0001). Carriers of the intermediate/high-level haplotype combination showed a bisected diabetes risk at the 3-year follow-up and were characterized by a "regression" of glucose tolerance. Evolution of disease status correlates with preexisting low adiponectin levels at inclusion rather than with variation in adiponectin levels. CONCLUSIONS: We present data that gene variants in the ADIPOQ promoter region are associated with variations in adiponectin levels and thus with future type 2 diabetes and disease progression.