Abstract
Preeclampsia represents one of the most frequent complications of pregnancy, however,
little is known about its aetiology. Damage of the endothelial layer lining the blood
vessel wall is thought to play an important role in the pathophysiology of preeclampsia,
accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among
preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in
preeclampsia by measuring plasma levels of homocysteine and studying the prevalence
of the 677(C→T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR)
gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma
homocysteine levels.
Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and
20 women with preeclampsia were analysed for total homocysteine levels by high performance
liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised
for preeclampsia and 403 population-based controls were analysed for the 677(C→T)
polymorphism by polymerase chain reaction followed by restriction fragment length
polymorphism analysis (PCR/RFLP).
In normotensive pregnancy homocysteine levels were lower compared with levels in healthy
non-pregnant controls (8.4 versus 13.7 μmol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive
pregnancy (13.3 versus 8.4 μmol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found
in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence
of the 677(C→T) polymorphism in the MTHFR gene between preeclamptic women with or
without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele,
respectively; OR 1.5, 95% CI 0.8–2.6, P=0.17).
In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia
is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in
preeclampsia might better be explained by fluctuations in plasma volume than by the
presence of the 677(C→T) polymorphism in the MTHFR gene.
Keywords
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© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.