GST polymorphisms and early-onset coronary artery disease in young South African Indians

Background. Glutathione S-transferases (GSTs) detoxify environmental agents which influence the onset and progression of disease. Dysfunctional detoxification enzymes are responsible for prolonged exposure to reactive molecules and can contribute to endothelial damage, an underlying factor in coronary artery disease (CAD).Objectives. We aimed to assess 2 common polymorphic variant isoforms in GSTM1 and GSTP1 of GST in young CAD patients.Methods. All patients (N=102) were South Africans of Indian ancestry, a population associated with high CAD risk. A corresponding age-, sex- and race-matched control group (N=100) was also recruited. Frequency of the GSTM1 +/0 (v. +/0 and 0/0) and GSTP1 A105/G105 (v. wild-type A105/A105) genotypes was assessed by differential polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP), respectively.Results. The GSTM1 0/0 and GSTP1 A105/A105 genotypes occurred at higher frequencies in CAD patients compared with the control group (36% v. 18% and 65% v. 48%, respectively). A significant association with CAD was observed in GSTM1 0/0 (odds ratio (OR)=2.593; 95% confidence interval (CI) 1.353 - 4.971; p=0.0043) and GSTP1 A105/A105 OR=0.6011; 95% CI 0.3803 - 0.9503; p=0.0377). We found a significant association between smoking and CAD; the presence of either of the respective genotypes together with smoking increased the CAD risk (GSTP1 A105 relative risk (RR)=1.382; 95% CI 0.958 - 1.994; p=0.0987 and GSTM1 null RR=1.725; 95% CI 1.044 - 2.851; p=0.0221).Conclusion. Our findings support the association of genotypes GSTM1 0/0 and GSTP1 A105/A105 and smoking with CAD.S Afr Med J 2012;102(7):627-630

Sirtuin 1 rs1467568 and rs7895833 in South African Indians with early-onset coronary artery disease

BACKGROUND : Sirtuin 1 (SIRT1), a class III histone deacetylase, has been identified as a candidate molecule affecting the epigenetic mechanisms of cardiovascular disease (CVD). Previous studies have shown that some SIRT1 single-nucleotide polymorphisms (SNPs) are associated with body mass index, diabetes, blood pressure, cholesterol metabolism and coronary artery calcification. We investigated two A>G SIRT1 SNPs, rs1467568 and rs7895833, in young South African (SA) Indians with coronary artery disease (CAD) and compared them to Indian and black controls. METHODS : For rs1467568, a total of 287 subjects were recruited into this study (104 CAD patients, 99 age-, gender- and race-matched controls, and 84 age- and gender-matched black controls). For rs7895833, a total of 281 subjects were recruited into this study (100 CAD patients, 99 age-, gender- and race-matched controls, and 82 age- and gender-matched black controls). All patients were male, of Indian ethnicity, stable CAD confirmed on angiography, mean age 37.5 years; range 24–45. All subjects were genotyped using TaqMan SNP genotyping assays. RESULTS : The variant allele for both SNPs was found at a higher frequency in the total Indian group compared to the total black population (rs1467568: 41 vs 18.5%, respectively, p < 0.0001, OR = 3.190, 95% CI: 2.058–40943; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.466, 95% CI: 1.620– 3.755). Indian controls presented with a higher frequency for both SNPs compared to black controls (rs1467568: 40 vs 18.5%, respectively, p < 0.0001, OR = 2.996, 95% CI: 1.850– 4.853; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.513, 95% CI: 1.578–4.004). No difference was seen in the distribution of both SNPs between CAD patients and either control group. We did not observe any association between the SNPs and clinical parameters in CAD patients and controls. CONCLUSION : Both SNP variant alleles occurred more frequently in SA Indians than in SA blacks. A larger study group and further analysis is required to assess whether these SIRT1 SNPs may serve as risk factors that contribute to Indians developing early-onset CAD.The National Research Foundation (NRF) for a scholarship and UKZN (College of Health Sciences).www.cvja.co.zaam2016Physiolog

TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment

T-helper (Th) 17 cells are a pro-inflammatory subset of CD4+ effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV. Our results show that TB+HIV+ pleurisy results in significantly reduced frequency of CD4+IL-17+RORC+STAT3+ Th17 cells compared to TB−HIV−ex vivo (p = 0.0054) and was confirmed in conditioned media studies in vitro (p = 0.0001). This was not associated with alterations in Th17 polarising cytokines IL-6, IL-21 and IL-23 or changes in Th17 signature cytokines IL-17A and F. However, the mRNA expression of Th17 signalling molecules, IL-6 (p = 0.0022), IL-6R (p = 0.0247), IL-1β (p = 0.0022) and signal transducer and activator (STAT) 3 (p = 0.0022) were significantly upregulated. Notably, TB+HIV+ pleural fluid contained significantly higher concentrations of IL-1β (p = 0.0008), IL-22 (p = 0.0115), IL-31 (p = 0.0210), TNF-α (p = 0.0251) and IFN-γ (p = 0.0026) than TB−HIV− pleural fluid ex vivo. Taken together, this suggests a reduced portion of Th17 lymphocytes in TB/HIV pleurisy is independent of locally mediated cytokine polarisation.The National Research Foundation, KwaZulu-Natal Research Institute for Tuberculosis and HIV and College of Health Sciences, University of KwaZulu-Natal.http://intl.elsevierhealth.com/journals/tube2017-07-31hb2016Physiolog

Sutherlandia frutescens: The meeting of science and traditional knowledge

Sutherlandia frutescens (L.) R.Br. (syn. Lessertia frutescens (L.) Goldblatt and J.C. Manning) is an indigenous medicinal plant extensively used in South Africa to treat a variety of health conditions. It is a fairly widespread, drought-resistant plant that grows in the Western, Eastern, and Northern Cape provinces and some areas of KwaZulu-Natal, varying in its chemical and genetic makeup across these geographic areas.1 Sutherlandia is widely used as a traditional medicine. Extensive scientific studies are being carried out on the safety, quality, and the efficacy of this medicinal plant to validate the traditional claims, elucidate the bioactive constituents, and conduct clinical trials. This has resulted in a unique situation in South Africa’s history, where traditional knowledge and science intersect to provide insight into this popular plant. This photoessay attempts to illustrate the interlinkage of science with the indigenous knowledge of traditional healers, the local knowledge of people who care for the sick, product development, and innovation agenda of the country as it relates to this plant.Web of Scienc

The effects of <i>Sutherlandia frutescens</i> extracts in cultured renal proximal and distal tubule epithelial cells

Sutherlandia frutescens (SF), a medicinal plant indigenous to South Africa, is traditionally used to treat a diverse range of illnesses, including cancer and viral infections. The biologically active compounds of SF are polar, thus renal elimination increases susceptibility to toxicity in that organ. This study investigated the antioxidant potential, lipid peroxidation, mitochondrial membrane potential and apoptotic induction by SF extracts on proximal and distal tubule epithelial cells. Cell viability was determined using the MTT assay. Mitochondrial membrane potential was determined using a flow cytometric JC-1 Mitoscreen assay. Cellular glutathione and apoptosis were measured using the GSH-Glo™ Glutathione assay and Caspase-Glo® 3/7 assay, respectively. The IC50 values from the cell viability results for LLC-PK1 and MDBK were 15 mg/mL and 7 mg/mL, respectively. SF extracts significantly decreased intracellular glutathione in LLC-PK1 (p < 0.0001) and MDBK (p < 0.0001) cells, while lipid peroxidation increased in treated LLC-PK1 (p < 0.0001) and MDBK (p < 0.0001) cells. JC-1 analysis showed that SF extracts promoted mitochondrial membrane depolarization in both LLC-PK1 and MDBK cells by up to 80% (p < 0.0001). The activity of caspase 3/7 increased in both LLC-PK1 (11.9-fold; p < 0.0001) and MDBK (2.2-fold; p < 0.0001) cells. SF extracts at high concentrations appear to increase oxidative stress, to alter mitochondrial membrane integrity, and to promote apoptosis in renal tubule epithelia

Platelet activation, apoptosis and parameters of endothelial dysfunction in type II diabetes mellitus and healthy controls

National Research Foundationhttps://drive.google.com/file/d/1b9eVgcEqWYOq64o-A55I5e27_G_Dv-uR/view?usp=sharinghttps://drive.google.com/drive/folders/1eplAGgCr9gjedFFNmuBvjOnHyU0RKjz-?usp=sharinghttps://drive.google.com/drive/folders/13zbuxDPJCGAoZLpIY6I0V9BKzesqbK6M?usp=sharin

Sirtuin 1 rs1467568 and rs7895833 in South African Indians with early-onset coronary artery disease

BACKGROUND : Sirtuin 1 (SIRT1), a class III histone deacetylase, has been identified as a candidate molecule affecting the epigenetic mechanisms of cardiovascular disease (CVD). Previous studies have shown that some SIRT1 single-nucleotide polymorphisms (SNPs) are associated with body mass index, diabetes, blood pressure, cholesterol metabolism and coronary artery calcification. We investigated two A>G SIRT1 SNPs, rs1467568 and rs7895833, in young South African (SA) Indians with coronary artery disease (CAD) and compared them to Indian and black controls. METHODS : For rs1467568, a total of 287 subjects were recruited into this study (104 CAD patients, 99 age-, gender- and race-matched controls, and 84 age- and gender-matched black controls). For rs7895833, a total of 281 subjects were recruited into this study (100 CAD patients, 99 age-, gender- and race-matched controls, and 82 age- and gender-matched black controls). All patients were male, of Indian ethnicity, stable CAD confirmed on angiography, mean age 37.5 years; range 24–45. All subjects were genotyped using TaqMan SNP genotyping assays. RESULTS : The variant allele for both SNPs was found at a higher frequency in the total Indian group compared to the total black population (rs1467568: 41 vs 18.5%, respectively, p < 0.0001, OR = 3.190, 95% CI: 2.058–40943; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.466, 95% CI: 1.620– 3.755). Indian controls presented with a higher frequency for both SNPs compared to black controls (rs1467568: 40 vs 18.5%, respectively, p < 0.0001, OR = 2.996, 95% CI: 1.850– 4.853; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.513, 95% CI: 1.578–4.004). No difference was seen in the distribution of both SNPs between CAD patients and either control group. We did not observe any association between the SNPs and clinical parameters in CAD patients and controls. CONCLUSION : Both SNP variant alleles occurred more frequently in SA Indians than in SA blacks. A larger study group and further analysis is required to assess whether these SIRT1 SNPs may serve as risk factors that contribute to Indians developing early-onset CAD.The National Research Foundation (NRF) for a scholarship and UKZN (College of Health Sciences).www.cvja.co.zaam2016Physiolog