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Research Publications (Health Sciences)

Permanent URI for this collectionhttp://ir-dev.dut.ac.za/handle/10321/216

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Author: search.filters.author.Asharam, KareshmaHas files: Yes

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    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.
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    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, Shivona
    The −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.
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    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, Shivona
    The 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.