Browsing by Author "Khaliq, Olive Pearl."
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Item Gene polymorphisms of uric acid related proteins and the Angiotensin Receptor IV (AT4) in Pre-eclampsia.(2019) Khaliq, Olive Pearl.; Naicker, Thajasvarie.; Moodley, Jagidesa.Background: Hypertensive disorders of pregnancy remain one of the major contributions to maternal and fetal morbidity and mortality around the globe. Pre-eclampsia is a hypertensive disorder of pregnancy which complicates 3-10% of pregnancies worldwide. It is a multi-organ disorder affecting the maternal system, thereby creating a major setback in terms of targeting the aetiology. One of the main organs disrupted is the kidneys and a dysregulation of uric acid levels and the renin angiotensin system have been implicated in pre-eclampsia. Therefore, the aim of this study is to investigate the gene polymorphisms of uric acid, aminopeptidase-N, the angiotensin receptor IV, and plasma levels of the receptor in pre-eclampsia compared to normotensive pregnancies. Materials and Methods: This was a retrospective study consisting of 637 blood samples of which 280 were normotensives and 357 pre-eclamptic. Pre-eclampsia was subdivided into early (n=187) and late onset pre-eclampsia (n=170). DNA was isolated from blood samples using the Thermo Scientific GeneJet whole blood Genomic DNA purification mini Kit. Single nucleotide polymorphisms of uric acid (rs505802, rs1014290, rs12129861, rs2231142), the angiotensin receptor IV (rs18059) and aminopeptidase-N (rs6496603) were amplified using the TaqMan genotyping assay. Plasma levels of angiotensin receptor IV were also measured using the ELISA in pre-eclampsia and compared to normotensives. Results: We found that rs505802 was higher in late onset pre-eclampsia compared to early onset pre-eclampsia and the normotensive group. We also observed a significant elevation of rs1014290 in early onset pre-eclampsia compared to late onset pre-eclampsia and the normotensive group. Gene polymorphisms of the angiotensin IV receptor (rs18059) and aminopeptidase-N (rs6496603) showed no significant association with pre-eclampsia. However, plasma levels of angiotensin IV receptor were significantly lower in pre-eclampsia than in normotensives. Furthermore, we found that the levels decreased with the severity of pre-eclampsia. Conclusion: The single nucleotide polymorphisms of uric acid (rs505802, rs1014290) are associated with the pathogenesis of pre-eclampsia. Furthermore, plasma levels of angiotensin IV are decreased in pre-eclampsia, indicating a dysregulation of the renin angiotensin system in pre-eclampsia. ABSTRACT-ISIZULU Amathuluzi asetshenzisiwe: Lolucwaningo lubizwa nge-retrospective lusebenzise amagazi awu 637 aphuma kwabanomfutho osesimweni sempilo (normotensives) abangu 280 Kanye nabanomfutho ophakeme wegazi kubakhulelwe (pre-eclamptic) abangu 357. Abanomfutho ophakeme wegazi baphinde bahlukaniswa izigaba ezimbili, ezibizwa nge early (n=187) ne late onset (n=170). Ufuzo egazini lutholakale ngokusebenzisa I Thermo Scientific GeneJet whole blood Genomic DNA purification mini Kit. Ama Single nucleotide polymorphisms e uric acid (rs505802, rs1014290, rs12129861, rs2231142), angiotensin receptor IV (rs18059) nawe aminopeptidase-N (rs6496603) acubulungwe ngokusebenzisa i- TaqMan genotyping assay. Izinga le-angiotensin receptor IV egazini likalwe ngokusebenzisa i-ELISA kwabanomfutho wamandla ophakeme kwabakhulelwe (pre-eclamptics) makuqhathaniswa nabanomfutho osesimweni sempilo (normotensive). Imiphumela: Sithole ukuthi amazinga e rs505802 abephezulu ku late onset pre-eclampsia makuqhataniswa ne early onset pre-eclampsia ne normotensive. Siphinde sabona ukukhuphuka kwenani le rs1014290 ku-early onset pre-eclampsia makuqhathaniswa ne late onset pre-eclampsia Kanye ne normotensive group. Ama gene polymorphisms we angiotensin IV receptor (rs18059) Kanye ne aminopeptidase-N (rs6496603) awakhombisanga mahluko ekuhlobaneni ne pre-eclampsia. Kodwa, inani le angiotensin IV receptor egazini abehlile kulabo abanomfutho wamadla ophakeme egazini (pre-eclampsia) makuqhathaniswa nalabo abanomfutho osesimweni sempilo (normotensive). Siphinde sathola ukuthi lokwehla kuhambisana nokubhebhetheka kwesifo somfutho wamadla ophakeme egazini. Ukuvala: I single nucleotide polymorphisms ye uric acid (rs505802, rs1014290) ihlobene nokuqala kwesifo somfutho wamadla ophakeme egazini kwabakhulelwe (pre-eclampsia). Futhi, izinga le angiotensin IV egazini lehlile kulabo abanomfutho wamadla ophakeme egazini kwabakhululwe (pre-eclampsia), okukhombisa ukungalawuleki kwe renin angiotensin system kulabo abanomfutho wamadla ophakeme egazini (pre-eclampsia).Item The role of mir-29a, mir-181a, and mir-222 in preeclamptic and gestational hypertensive patients.(2017) Khaliq, Olive Pearl.; Mackraj, Irene.Backgrounds Hypertensive disorders of pregnancy, a major cause of maternal and neonatal morbidity worldwide are characterized by widespread maternal endothelial dysfunction and metabolic disorders (blood pressure and insulin resistance). Dysregulation in proteins (AKT and PI3K) involved in the insulin signaling pathway lead to insulin resistance, which is a common feature in the second half of most pregnancies complicated by preeclampsia and gestational hypertension. The objective of this study was to quantify microRNAs in serum and placental tissue of women with gestational hypertension (GH) and preeclampsia (PE). Methods This study is a prospective cross-sectional study involving 32 normotensive pregnant women (control), 32 women with preeclampsia (PE) and 28 with gestational hypertension (GH). The patients were recruited from a regional hospital in Durban, KwaZulu-Natal Province, South Africa. Serum and placental microRNA were quantified using RT-qPCR to compare levels of expression in the control, PE, and GH. In addition, a western blot analysis was carried out to investigate the levels of protein expression (AKT and PI3K) in the insulin signaling pathway. Results Serum, miRNA-222 quantitative real-time PCR expression levels were significantly lower in PE compared to normotensives (p=0.0186). miR-29 expression levels were significantly higher in PE (p<0.0001) and GH (p<0.0001) groups compared to normotensives. miR-181a serum expression levels of GH were significantly higher compared to normotensives (p=0.0070). Placental tissue expression showed significantly higher expression levels of miR-181a in PE (p=0.0344) and GH (p=0.0344) groups compared to normal controls. Western blot analysis of proteins showed a lower expression of AKT-serine and threonine in the PE (p=0.0001) compared to the normal control groups and significantly higher expression in the GH (p=0.0001) groups compared to the normal controls. Furthermore, the expression of the phosphatidyl-inositol-3 kinase (PI3K) was statistically lower in PE (p=0.0001) and GH (p=0.0001) compared to the normal controls. Discussion/Conclusion MicroRNAs may be used as potential biomarkers for PE and GH. The results of this study showed a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the existence of metabolic dysregulation in PE and GH