A study protocol for a cluster randomized controlled trial to test the applicability of the South African diabetes prevention program in the Eastern Cape Province of South Africa.

Background: Convincing evidence supports the effectiveness of lifestyle interventions in preventing the occurrence of diabetes in high-income countries, however little is known about appropriate interventions for use in African countries, where there are higher relative increases in diabetes prevalence. The South African Diabetes Prevention Programme (SA-DPP) was initiated with the aim of preventing or delaying the occurrence of diabetes among South Africans (SAs), through interventions, targeting lifestyle changes related to diet and physical activity. The purpose of the current project is to implement and evaluate the suitability and applicability of the SA-DPP developed and tailored in urban populations in the Western Cape Province, in peri-urban populations in the Eastern Cape Province of SA.

Pancreatic ductal adenocarcinoma: Prognostic indicators of advanced disease.

Background/objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with high metastatic risk. Prognosis remains poor even after resection. Previously our group identified biomarkers that improved diagnostic accuracy in PDAC beyond the established diagnostic tumour marker, CA19-9.

Inflammatory cytokines and combined biomarker panels in pancreatic ductal adenocarcinoma: Enhancing diagnostic accuracy.

Background: Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenged by the absence of accurate early diagnostic and prognostic biomarkers. CA19-9 is the established, diagnostic tumour marker in PDAC, despite its limitations. Effective primary screening using circulating biomarker panels have only been considered in a handful of studies and we investigated whether combinations of inflammatory cytokines and angiogenic factors in multivariate logistic models could facilitate earlier diagnosis in our South African setting.

An African perspective on the genetic risk of chronic kidney disease: a systematic review.

Background: Individuals of African ethnicity are disproportionately burdened with chronic kidney disease (CKD). However, despite the genetic link, genetic association studies of CKD in African populations are lacking.

Methods: We conducted a systematic review to critically evaluate the existing studies on CKD genetic risk inferred by polymorphism(s) amongst African populations in Africa.

MicroRNA profiling and their pathways in South African individuals with prediabetes and newly diagnosed type 2 diabetes mellitus.

Early identification of individuals with elevated risk of developing diabetes mellitus, followed by the implementation of effective prevention interventions can delay the onset of the disease and related complications. In this regard, recent studies have shown that miRNAs are useful as early markers of certain disease types, including diabetes. We used high throughput sequencing to assess miRNA expression profiles from whole blood of 12 individuals with screen-detected diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for age, blood pressure, smoking and body mass index.

Genetic factors contributing to hypertension in African-based populations: A systematic review and meta-analysis.

In a systematic review, the authors explored genetic association studies of essential hypertension in African populations. Studies reporting on the association of polymorphism(s) with hypertension in African populations were included. Appropriate studies were pooled using random effects model meta-analysis, under six potential inheritance models.

Inflammatory cytokines and angiogenic factors as potential biomarkers in South African pancreatic ductal adenocarcinoma patients: A preliminary report.

Background/objectives: Several studies have investigated the association of differentially expressed cytokines with pancreatic ductal adenocarcinoma (PDAC), but none in African countries. This study aimed at investigating T-helper (Th) cell and angiogenic markers as diagnostic or prognostic biomarkers for PDAC in Black South Africans.

Methods: We conducted a prospective, case-control study comprising of 34 PDAC patients and 27 control participants with either critical limb ischemia, abdominal aortic aneurysm or other abdominal pathology from causes other than pancreatic disease.

Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Objectives: A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken.

Materials And Methods: A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles.

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.

Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations.

Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population.

Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits.

Genetic risk of type 2 diabetes in populations of the African continent: A systematic review and meta-analyses.

Background: Type 2 diabetes (T2D) is growing faster in Africa than anywhere else, driven by the dual effects of genetic and environmental factors. We conducted a systematic review and meta-analyses of published studies on genetic markers of T2D in populations within Africa.

Methods: Multiple databases were searched for studies of genetic variants associated with T2D in populations living in Africa.

APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans.

Background: The frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures.

Air pollution and risk of type 2 diabetes mellitus: a systematic review and meta-analysis.

Aim: Whether exposure to relatively high levels of air pollution is associated with diabetes occurrence remains unclear. We sought to assess and quantify the association between exposure to major air pollutants and risk of type 2 diabetes.

Methods: PubMed and EMBASE databases (through September 2013) were searched using a combination of terms related to exposure to gaseous (NO2 and NOx) or particulate matter pollutants (PM2.

Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa.

Background: The peroxisome proliferator-activated receptor gamma (PPARG), Pro12Ala and the insulin receptor substrate (IRS1), Gly972Arg confer opposite effects on insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the independent and joint effects of PPARG Pro12Ala and IRS1 Gly972Arg on markers of insulin resistance and T2DM in an African population with elevated risk of T2DM. In all 787 (176 men) mixed-ancestry adults from the Bellville-South community in Cape Town were genotyped for PPARG Pro12Ala and IRS1 Gly972Arg by two independent laboratories.

Optimal waist-to-height ratio values for cardiometabolic risk screening in an ethnically diverse sample of South African urban and rural school boys and girls.

Background: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value.

Gamma-glutamyltransferase, insulin resistance and cardiometabolic risk profile in a middle-aged African population.

Background: Mechanisms linking liver functions with cardiometabolic risk may involve insulin resistance (IR) and non-alcoholic fatty liver disease. We assessed the associations of gamma-glutamyltransferase (GGT) levels with IR and metabolic syndrome (MetS) in an adult South African urban cohort.

Methods: 1198 participants aged >15 years (297 men) were drawn from the Bellville-South suburb (Cape Town).

Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators.

Background: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa.

Methods: Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town.

Polymorphisms in the non-muscle myosin heavy chain gene (MYH9) are associated with lower glomerular filtration rate in mixed ancestry diabetic subjects from South Africa.

Objective: Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes.

Research Design And Methods: Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town.

Associations of MC3R polymorphisms with physical activity in South African adolescents.

Background: There is evidence demonstrating that the contribution of sedentary behavior and effect of physical activity on metabolic phenotypes is mediated by polymorphisms in genes.

Methods: The type and frequency of physical activity was assessed by means of structured questionnaires in 1555 South African school learners. Anthropometric measurements, blood pressure, fasting blood glucose and lipids were measured using standard procedures.

CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application.

Approximately 25% of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status.

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.

Molecular analysis of the parkin gene in South African patients diagnosed with Parkinson's disease.

Parkinson's disease (PD) is a common movement disorder which may arise from mutations in the parkin gene. To date, more than 100 different parkin mutations have been reported. The aim of the present study was to determine the frequency of point mutations and homozygous exon deletions in the parkin gene in a group of 91 South African patients diagnosed with PD.