Solute carrier transporters: Pharmacogenomics research opportunities in Africa

Membrane transporters play a critical role in drug response as they provide the targets for many commonly used drugs and are major determinants of drug absorption, distribution, and elimination. Most of them belong to one of the two major super-families of membrane transport proteins, the ATPbinding cassette (ABC) transporters, and the solute carrier (SLC) transporters. They are subject to both genotypic and phenotypic polymorphisms, and variation in drug transporters may be the reason for inter-individual variability in pharmacokinetic disposition, efficacy, and toxicity of drug transporter substrates. The growing number of publications reporting genetic population data for the solute carriertransporters in particular shows their importance, as well as the increased interest in investigating them in most recent pharmaco-genetics/ genomics research projects. These publications range from reporting baseline frequency distributions of SNPs of genes important in drug transport, discovering new genetic variants of these genes, and/or describing genotyping projects to identify probable responders or non-responders to therapy, or to predict exposure levels in different patients. This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from characterizing human genomic variation in South Africa and sub-Saharan Africa, especially with regards to health applications. Genomic diversity in this region is indeed relatively under-studied despite being home to significant portion of human genomic diversity.Keywords: Solute carrier transporters, pharmacogenomics, pharmacogenetic

Use of molecular genetics and historical records to reconstruct the history of local communities

Recent advances in molecular genetics made the inference of past demographic events through the analysis of gene pools from modern populations possible. The technology uses genetic markers toprovide previously unavailable resolution into questions of human evolution, migration and the historical relationship of separated human populations. Some of the genetic markers used to measurevariation (polymorphism) within populations are found in the Y-chromosome and mitochondrial DNA. Variations in these two types of DNA can be grouped into continent-specific haplogroups or lineages.Geographic origin can be assigned to each lineage, and consequently trace back migration pattern of human populations. Y-chromosome and mitochondrial DNA are used to construct paternal and maternal lineages respectively. The use of these molecular techniques together with historical records in an integrated manner can greatly benefit the study of the social history of admixed communities, such as the Cape Muslim community living in the Western Cape of South Africa

Methylenetetrahydrofolate Reductase Polymorphism (rs1801133) and the Risk of Hypertension among African Populations: A Narrative Synthesis of Literature

In this review, we have gathered and analyzed the available genetic evidence on the association between the methylenetetrahydrofolate reductase gene (MTHFR), rs1801133 and the risk of Hypertension (HTN) in African populations, which was further compared to the global data evidence. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and Human Genome Epidemiology Network (HuGENet) guidelines. Literature was retrieved through major search databases, including PubMed, Scopus, Web of Science, and African Journal Online. We identified 64 potential studies, of which 4 studies were from the African continent and 60 studies were reported globally. Among the studies conducted in Africa, only two (n = 2) reported a significant association between the MTHFR (rs1801133) and the risk of developing HTN. Only one (n = 1) study population was purely composed of black Africans, while others were of other ethnicities. Among studies conducted in other continents (n = 60), forty seven (n = 47) studies reported a positive association between MTHFR (rs1801133) and the risk of developing HTN, whereas the remaining studies (n = 14) did not show a significant association. Available literature suggests an apparent association between rs1801133 and HTN in global regions; however, such information is still scarce in Africa, especially in the black African population

Prevalence of hypertension and its associated risk factors in a rural black population of Mthatha town,South Africa

The occurrence of hypertension has been increasing alarmingly in both low and middle-income countries. Despite acknowledging hypertension as the most common life-threatening risk factor for cardiovascular disease (CVD), a dearth of data is available on the prevalence, awareness, and determinants of hypertension in rural parts of South Africa. The principal aim of the current study is to determine the prevalence and associated risk factors of hypertension among a black rural African population from the Mtatha town of Eastern Cape Province. Methods: This was a cross-sectional study, and individuals over 18 years of age were randomly screened using a World Health Organization stepwise questionnaire. Sociodemographic information, anthropometric measurements, fasting blood glucose levels, and three independent blood pressure (BP) readings were measured. Blood pressure measurements were classified according to the American Heart Association guidelines. Univariate and multivariate analyses were performed to determine the significant predictors of hypertension. Results: Of the total participants (n = 556), 71% of individuals had BP scores in the hypertensive range. In univariate analysis, age, westernized diet, education, income, and diabetic status, as well as overweight/obese status were positively associated with the prevalence of hypertension

Cross-sectional study of prevalence and determinants of uncontrolled hypertension among South African adult residents of Mkhondo municipality

Background: Achieving the blood pressure treatment target in individuals with hypertension is a serious global health challenge. Furthermore, the actual burden of uncontrolled hypertension is poorly understood, especially in the developing countries. Therefore, this study comprehensively examined the prevalence and factors associated with uncontrolled hypertension in individuals receiving care at the primary healthcare facilities in the rural areas of Mkhondo Municipality in the Mpumalanga Province, South Africa. Methods: In this cross-sectional study, 329 individuals attending care for hypertension were recruited from January 2019 to June 2019 at three primary healthcare centres, namely, Piet Retief hospital, Mkhondo town clinic and Thandukukhanya community health centre. Uncontrolled hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg in accordance with the South African Hypertension Society guideline (2014). Multiple logistic regression (Forward LR method) analysis was used to identify the significant determinants of uncontrolled hypertension. Results: The majority of the participants were 55 years old and above (69.0%), Zulus (81.2%), non-smokers (84.19%) and had been diagnosed with hypertension for more than a year prior to the study (72.64%). The overall prevalence of uncontrolled hypertension was 56.83% (n = 187) with no significant difference between sexes, 57.38% male versus 56.88% female, respectively. In the multiple logistic regression model analysis after adjusting for confounding variables, obesity (AOR = 2.90; 95% CI 1.66–5.05), physical activity (AOR = 4.79; 95% CI 2.15–10.65) and HDL-C (AOR = 5.66; 95% CI 3.33–9.60) were the significant and independent determinants of uncontrolled hypertension in the cohort. Conclusion: The high prevalence of uncontrolled hypertension in the study setting can be largely attributed to obesity, physical activity and dyslipidaemia. Treatment will require the collaborative efforts of individuals, clinicians and health authorities. All these determinants should be addressed decisively so as to achieve the treatment blood pressure targets in the study population

Cross-sectional study of prevalence and determinants of uncontrolled hypertension among South African adult residents of Mkhondo municipality

Background: Achieving the blood pressure treatment target in individuals with hypertension is a serious global health challenge. Furthermore, the actual burden of uncontrolled hypertension is poorly understood, especially in the developing countries. Therefore, this study comprehensively examined the prevalence and factors associated with uncontrolled hypertension in individuals receiving care at the primary healthcare facilities in the rural areas of Mkhondo Municipality in the Mpumalanga Province, South Africa. Methods: In this cross-sectional study, 329 individuals attending care for hypertension were recruited from January 2019 to June 2019 at three primary healthcare centres, namely, Piet Retief hospital, Mkhondo town clinic and Thandukukhanya community health centre. Uncontrolled hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg in accordance with the South African Hypertension Society guideline (2014). Multiple logistic regression (Forward LR method) analysis was used to identify the significant determinants of uncontrolled hypertension. Results: The majority of the participants were 55 years old and above (69.0%), Zulus (81.2%), non-smokers (84.19%) and had been diagnosed with hypertension for more than a year prior to the study (72.64%). The overall prevalence of uncontrolled hypertension was 56.83% (n = 187) with no significant difference between sexes, 57.38% male versus 56.88% female, respectively. In the multiple logistic regression model analysis after adjusting for confounding variables, obesity (AOR = 2.90; 95% CI 1.66–5.05), physical activity (AOR = 4.79; 95% CI 2.15–10.65) and HDL-C (AOR = 5.66; 95% CI 3.33–9.60) were the significant and independent determinants of uncontrolled hypertension in the cohort. Conclusion: The high prevalence of uncontrolled hypertension in the study setting can be largely attributed to obesity, physical activity and dyslipidaemia. Treatment will require the collaborative efforts of individuals, clinicians and health authorities. All these determinants should be addressed decisively so as to achieve the treatment blood pressure targets in the study population

Reconstruction of major maternal and paternal lineages of the Cape Muslim population

The earliest Cape Muslims were brought to the Cape (Cape Town - South Africa) from Africa and Asia from 1652 to 1834. They were part of an involuntary migration of slaves, political prisoners and convicts, and they contributed to the ethnic diversity of the present Cape Muslim population of South Africa. The history of the Cape Muslims has been well documented and researched however no in-depth genetic studies have been undertaken. The aim of the present study was to determine the respective African, Asian and European contributions to the mtDNA (maternal) and Y-chromosomal (paternal) gene pool of the Cape Muslim population, by analyzing DNA samples of 100 unrelated Muslim males born in the Cape Metropolitan area. A panel of six mtDNA and eight Y-chromosome SNP markers were screened using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). Overall admixture estimates for the maternal line indicated Asian (0.4168) and African mtDNA (0.4005) as the main contributors. The admixture estimates for the paternal line, however, showed a predominance of the Asian contribution (0.7852). The findings are in accordance with historical data on the origins of the early Cape Muslims.Web of Scienc