Faculty of Health Sciences
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Item Interaction between ambient pollutant exposure, CD14 (-159) polymorphism and respiratory outcomes among children in Kwazulu-Natal, Durban(Sage Publishing, 2016) Makamure, Michelle T.; Reddy, Poovendhree; Chuturgoon, Anil A.; Naidoo, Rajen N.; Mentz, Graciela; Batterman, Stuart; Robins, Thomas G.The objective of this study was to determine if the association between exposure to ambient air pollutants such as sulfur dioxide, nitrogen dioxde (NO2), nitrous oxide (NO), and PM10, and variation in lung function measures was modified by genotype. A validated questionnaire was administered to 71 African children to evaluate prevalence of respiratory symptoms. Atopy was evaluated by skin-prick testing and bihourly measures of lung function (spirometry) were collected. Gaseous air pollutant concentrations were monitored continuously. CD14 polymorphism was genotyped and plasma CD14 levels were measured. There was no statistically significant association between the CD14 (159) CTþTT polymorphism with any asthma-related phenotype. There was a significant association between lung function (forced expiratory volume in 1 second intraday variability) and NO2 and NO among participants carrying the CD14 CT/TT genotype for lags 1, 2, and the 5-day average. Similarly, statistically significant gene–pollutant interactions (p < 0.05) were found with NO and CD14 CT/TT at lag 2 and for the 5-day average. While there was no association with any respiratory phenotype (as determined by symptoms), the CD14 CT/TT genotype appeared to be protective to increased exposure to NO2 and NO.Item Prenatal exposures and DNA methylation in newborns: A pilot study in Durban, South Africa(Royal Society of Chemistry, 2016) Goodrich, Jaclyn M.; Reddy, Poovendhree; Naidoo, Rajen N.; Asharam, Kareshma; Batterman, Stuart; Dolinoy, Dana C.The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.Item Tumour necrosis factor α polymorphism (TNF-308α G/A) in association with asthma related phenotypes and air pollutants among children in KwaZulu-Natal(Thai Health Science Journals, 2016-09) Makamure, Michelle T.; Reddy, Poovendhree; Chuturgoon, Anil A.; Naidoo, Rajen N.; Mentz, Graciela; Batterman, Stuart; Robins, Thomas G.BACKGROUND: The study of gene-environment interactions enables us to further understand the pathogenesis of asthma and inflammation. The TNF-α gene has been associated with airway pathology in asthma but there is limited information in relation to pollutant exposure and the TNF-α 308G/A polymorphism. OBJECTIVE: To determine the risk conferred by the TNF-α 308(G/A) polymorphism on respiratory outcome and to evaluate whether the association between exposure to ambient air pollutants such as SO2, NO2, NO, and PM10 and variation in lung function measures is modified by genotype. METHODS: The sample comprised 129 African children (between 9-11 years old). A questionnaire based on guidelines from the British Medical Research Council and the American Thoracic Society was administered to all caregivers to evaluate the prevalence of respiratory symptoms. Atopy was evaluated by skin prick testing. Bihourly measures of lung function (spirometry) were collected at school five days per week over three week periods in each of four seasons (2004-2005) using digital hand-held devices. During each of the four intensive 3-week phases, gaseous air pollutant concentrations were monitored continuously. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-PFLP) analysis was used to detect the TNF-α 308 genotype and plasma TNF-α levels were measured using the human TNF-α Max Standard™ Enzyme-linked immuno-absorbent assay (ELISA) kit. RESULTS: The TNF-α variant A allele was common among this sample of African children (40% with an allelic frequency of 0.24). There was no significant association with the TNF-α G/A polymorphism and any respiratory linked phenotype, nor cytokine levels. However, when exposure to pollutants were analyzed with genotypic and phenotypic data, we found relatively modest interaction effects for the TNF-α 308 genotype. GEE models showed that children with the TNF-α 308 A allele had increased deterioration of lung function post pollution exposure to SO2 [β=2.62, CI:0.51-4.71, p=0.02 and pint=0.03] and NO [β=3.28, CI:0.68-5.89, p=0.01, pint=0.03]. CONCLUSION: The TNF-α 308 (G/A) polymorphism may be associated with increased pollutant-associated effects on FEV1 intraday variability for both SO2 and NO. The A allele may increase susceptibility to the adverse effects of air pollutants.Item Effect of the TNF α-308 polymorphism on birth outcomes among South African women(JABS, 2014-04) Reddy, Poovendhree; Naidoo, Rajen N.; Chuturgoon, Anil A.; Asharam, Kareshma; Phulukdaree, Alisa; Gounden, ShivonaThe −308 G/A promoter polymorphism in the tumor necrosis factor-alpha (TNF- α) gene has been extensively studied as a potential biomarker for pregnancy outcomes, but results tend to be population specific. The aim of this study was to evaluate the association of the TNF α-308 polymorphism with preterm birth (PTB) and low birth weight (LBW) in a cohort of South African women enrolled in a prospective pregnancy study. The Mother and Child Environmental cohort (MACE) pilot study was done in Durban, KwaZulu-Natal during 2010-2011 with 100 pregnant women recruited. Demographic, exposure and prenatal clinical data was collected during the third trimester, maternal and infant hospital records at delivery were reviewed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the TNF-α -308 genotype. Plasma TNF-α concentration was measured using the human TNF-α Max Standard™ ELISA kit (Bio-legend). The polymorphic TNF-α GA+AA genotype was found among 35% of mothers. Mean birth weight was significantly lower among mothers with the TNF-α AG+AA genotype (p<0.05). Mothers who delivered LBW infants (<2500g) showed a significantly higher mean TNF- α level compared to mothers with normal birth weight deliveries. In addition, mothers with the TNF-α AG+AA genotype had a statistically significant drop in birth weight (β= -273.6; SE105.8; CI: -0.9,-1.35). While the TNF-α A allele was not associated with PTB, it was significantly associated with low birth weight in this study. Early identification of such immunological biomarkers may facilitate prevention of adverse pregnancy outcomes.Item GSTM1, GSTP1 and NQO1 polymorphisms and susceptibility to asthma among South African children(SAJEI, 2012) Reddy, Poovendhree; Naidoo, Rajen N.; Robins, Thomas G.; Mentz, Graciela; Li, Huiling; London, Stephanie J.Gluthathione-S-transferase (GSTM1 and GSTP1) and nicotinamide quinone oxidoreductase (NQO1) genes play an important role in cellular protection against oxidative stress, which has been linked to asthma pathogenesis. We investigated whether common, functional polymorphisms in GSTM1, GSTP1, and NQO1 influence susceptibility to asthma among schoolchildren in South Africa. Genomic deoxyribonucleic acid (DNA) was extracted from 317 primary schoolchildren, aged 9-11 years, from the urban, underprivileged socio-economic communities of Durban. GSTM1 (null vs. present genotype), GSTP1 (Ile105Val; AA →AG+GG) and the NQO1 (Pro/Ser; CC →CT/TT) genotypes were determined using polymerase chain reaction. Among the children, 30% were GSTM1 null, 65% carried the G allele for GSTP1, and 36% carried the C allele for NQO1.There was a high prevalence of asthma of any severity (46.1%), with 20.4% reporting persistent asthma. The GSTP1 AG+GG polymorphic genotype was significantly associated with persistent asthma (adjusted OR = 3.98; CI = 1.39, 11.36, p-value = 0.01). Neither the GSTM1, nor the NQO1, genotype was a significant predictor of persistent asthma. Therefore, the GSTP1 A/G variant may modulate the risk of persistent asthma among our sample.Item Correlation between glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase pi gene (GSTP1) polymorphisms and markers of inflammatory stress in pregnant females(Academic Journals, 2013-03) Reddy, Poovendhree; Naidoo, Rajen N.; Chuturgoon, Anil A.; Asharam, Kareshma; Naidoo, Dhaneshree; Phulukdaree, Alisa; Gounden, ShivonaThe Mother and Child Environmental Cohort (MACE) study piloted in South Africa in 2010 to 2011, collected genetic, biochemical and clinical data from pregnant females residing in south and north Durban. We evaluated birth outcomes and the influence of GSTM1pos→GSTM1null and the GSTP1 (Ile105Val; AA→AG/GG) polymorphisms on the extent of DNA damage and with biomarkers [glutathione (GSH) and malondialdehyde (MDA)] related to oxidative stress in mothers with different levels of pollutant exposure. There was no significant difference in adverse birth outcomes or genotype distribution between mothers from the exposed and lower exposed areas. Mean GSH and comet tail length did not differ significantly between GSTM1pos and GSTM1null genotypes. When stratified by genotype, mean MDA levels was higher among GSTM1 null mothers compared to the GSTM1pos mothers (p = 0.01). When each of the genotypes was stratified by exposure, mean GSH concentration was significantly higher in north Durban for the GSTM1pos, GSTM1null and GSTP1AG+GG genotypes (p < 0.05), and mean comet tail length was significantly increased in south Durban among participants with the GSTM1pos, GSTM1null, and the GSTP1AG+GG genotypes. The expression of GSTM1 and GSTP1 polymorphic genotypes may lead to varying susceptibility to the adverse effects of pollutants by modifying the response to oxidative stress.