Gene polymorphisms of uric acid related proteins and the Angiotensin Receptor IV (AT4) in Pre-eclampsia.

Abstract

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).