Genetic aspects of pre-eclampsia : mutation screening of the low-density lipoprotein receptor, methylenetetrahydrofolate reductase, prothrombin and factor V candidate genes

[摘要] ENGLISH ABSTRACT:Pre-eclampsia is a condition unique to pregnancy and primarily affects the maternaland placental vascular endothelium. It has significant morbidity and mortalityconsequences for both mother and infant. Despite global research into the aetiologyof the condition, the cause for this condition remains unknown. Several factors,including a strong family history of hypertension in pregnancy point to a familial orgenetic component in the pathophysiology of this complication.The purpose of this research project was to investigate candidate genes implicated inendothelial damage. Common methylene-tetra-hydrofolate reductase (MTHFR) genemutations C677T and A1298C, factor V Leiden mutation R506Q and prothrombinmutation A20210G were investigated in 50 patients with an uncomplicated pregnancyoutcome (controls) and 350 patients with various clinical manifestations of preeclampsia,including severe, early onset forms and abruptio placentae. Fastinghomocystein levels were determined biochemically on all participants.In addition, 126 consecutive pregnant patients were recruited at booking, fastinglipograms were performed on them as well as mutation screening of 7 commonmutations in the low-density lipoprotein receptor gene. This was correlated witheventual pregnancy outcome, and those with an uncomplicated outcome wereselected as an additional control group.A significant association between hyperhomocysteinaemia and early onset severepre-eclampsia could be demonstrated. Mutant allele T of the C677T mutation couldbe associated with hyperhomocysteinaemia but not with pre-eclampsia whilst mutantallele C of mutation A1298C demonstrated a significant correlation with diastolic blood pressure. In addition, combined heterozygosity for these mutations may serveas a marker for abruptio placentae.

[发布机构] Stellenbosch University