Thesis (MSc)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Pre-eclampsia is a condition unique to pregnancy and primarily affects the maternal
and placental vascular endothelium. It has significant morbidity and mortality
consequences for both mother and infant. Despite global research into the aetiology
of the condition, the cause for this condition remains unknown. Several factors,
including a strong family history of hypertension in pregnancy point to a familial or
genetic component in the pathophysiology of this complication.
The purpose of this research project was to investigate candidate genes implicated in
endothelial damage. Common methylene-tetra-hydrofolate reductase (MTHFR) gene
mutations C677T and A1298C, factor V Leiden mutation R506Q and prothrombin
mutation A20210G were investigated in 50 patients with an uncomplicated pregnancy
outcome (controls) and 350 patients with various clinical manifestations of preeclampsia,
including severe, early onset forms and abruptio placentae. Fasting
homocystein levels were determined biochemically on all participants.
In addition, 126 consecutive pregnant patients were recruited at booking, fasting
lipograms were performed on them as well as mutation screening of 7 common
mutations in the low-density lipoprotein receptor gene. This was correlated with
eventual pregnancy outcome, and those with an uncomplicated outcome were
selected as an additional control group.
A significant association between hyperhomocysteinaemia and early onset severe
pre-eclampsia could be demonstrated. Mutant allele T of the C677T mutation could
be associated with hyperhomocysteinaemia but not with pre-eclampsia whilst mutant
allele C of mutation A1298C demonstrated a significant correlation with diastolic blood pressure. In addition, combined heterozygosity for these mutations may serve
as a marker for abruptio placentae. / ENGLISH ABSTRACT: Pre-eklampsie is 'n hipertensiewe toestand uniek aan menslike swangerskap en dit
affekteer hoofsaaklik die vaskulêre endoteel. Die toestand hou ernstige morbiditeit en
mortaliteit vir beide ma en baba in en na jare se navorsing is die oorsaak van hierdie
toestand steeds onbekend. Epidemiologiese studies toon 'n duidelike familiële
verband aan wat die vermoede laat ontstaan dat daar 'n onderliggende genetiese
aspek tot die ontwikkeling van die siektetoestand is.
Die doel van hierdie navorsingsprojek was om gene te ondersoek wat geïmpliseer
word in endoteel skade. Twee algemene mutasies, C677T en A1298C in die MTHFR
geen asook faktor V Leiden R506Q en protrombien A20210G mutasies is ontleed in
50 pasiënte met 'n ongekompliseerde swangerskapsverloop en in 350 pasiënte met
'n swangerskap gekompliseer deur verskillende kliniese manifestasies van die
siekteproses, insluitende vroeë aankoms erge pre-eklampsie en abruptio placentae.
Op alle pasiënte is ook 'n vastende homosistiën vlak biochemies bepaal.
'n Verdere 126 opeenvolgende pasiënte is gewerf tydens hulle eerste besoek aan die
voorgeboortekliniek en vastende lipogramme is op almal uitgevoer. Mutasie sifting vir
7 algemene mutasies in die lae-digtheids lipoproteïen reseptor geen is op hierdie
groep gedoen en die resultaat is met die uiteindelike swangerskapsuitkoms
gekorreleer. Pasiënte met 'n uitkoms ongekompliseer deur hipertensie is gekies om
deel te wees van 'n verdere kontrolegroep.
Daar was 'n betekenisvolle verband tussen hiperhomositiënemie en erge, vroeë
aankoms pre-eklampsie. Die T alleel van die C677T mutasie is geassosieer met
hiperhomosistiënemie maar nie met pre-eklampsie nie. Die C alleel van die A 1298C
mutasie toon 'n betekenisvolle verband met diastoliese bloeddruk. Gekombineerde heterosigositeit vir beide MTHFR mutasies kan 'n moontlike merker vir abruptio
placentae wees.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/52284 |
| Date | 03 1900 |
| Creators | Gebhardt, G. S. |
| Contributors | Odendaal, H. J., Hillermann, R., Kotze, M. J., Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Pathology. Anatomical Pathology. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 168 p. : ill. |
| Rights | Stellenbosch University |
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