In black south africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1 act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1 act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT

Predictive utility of a genetic risk score of common variants associated with type 2 diabetes in a black South African population

Aims To determine the predictive utility of polygenic risk scores of common variants associated with type 2 diabetes derived from the European and Asian ethnicities among a black South African population. Method Our study was a case-control study nested within the Prospective Urban and Rural Epidemiological (PURE) study of 178 male and female cases, matched for age and gender with 178 controls. Four types of genetic risk scores (GRS) were developed from 66 selected SNPs. These comprised of beta cell related variants (GRSb), variants which had significant associations with T2D in our study (GRSn), variants from the trans-ethnic meta-analysis (GRStrans) and all the 66 selected SNPs (GRSt). Results Of the GRS’s, only GRSn was associated with increased risk of T2D as indicated by an OR (95CI) of 1.21 (1.02–1.43) p-value = 0.015. Stratified analysis of age and BMI, indicated the GRSn to be significantly associated with T2D among the non-obese and participants less than 50 years. The area under the ROC of the T2D risk factors only was 0.652 (p value < 0.001) and with the addition of GRSn it was 0.665 (p value < 0.001). Conclusions The GRS of European and Asian derived variants have limited clinical utility in the black South African population. The inclusion of population specific variants in the GRS is pivotal

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

Response of the microbial community to copper oxychloride in acidic sandy loam soil

Aims: Determining the response of different microbial parameters to copper oxychloride in acidic sandy loam soil samples using cultivation-dependent and direct microscopic techniques. Methods and Results: Culturable microbial populations were monitored for 245 days in a series of soil microcosms spiked with different copper oxychloride concentrations. Microbial populations responded differently to additional Cu. Protistan numbers and soil metabolic potential decreased. Experiments with more soil samples revealed that metabolic potential was not significantly affected by ≤100 mg kg-1 additional Cu. However, a negative impact on protista was noted in soil containing only 15 mg kg-1 EDTA-extractable Cu. The negative impact on protistan numbers was less severe in soils with a higher phosphorous and zinc content. Conclusions: Bacterial populations responded differently, and protista were most sensitive to elevated Cu levels. Protistan numbers in soil from uncultivated land were higher and seemed to be more sensitive to additional Cu than the numbers of these organisms in soil originating from cultivated land. Significance and Impact of the Study: Protistan sensitivity to small increases in Cu levels demonstrates the vulnerability of the soil ecosystem to Cu perturbations, especially when the importance of protista as link in the flow of energy between trophic levels is considered. © 2005 The Society for Applied Microbiology.Articl

Interactions between C-reactive protein genotypes with markers of nutritional status in relation to inflammation

Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications. Methods: ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery. Results: The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784. Conclusions: This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance. © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Medical Research Council of South Africa gran