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a Department of
Obstetrics and Gynaecology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands, b Department of Gastroenterology,
University Hospital Nijmegen, The Netherlands, c Department of Obstetrics
and Gynaecology, University Hospital Rotterdam, The Netherlands
Correspondence to: Dr Steegers, E.Steegers{at}obgyn.azn.nl
Revised version received 30 November 2000;
Accepted for publication 17
January 2001
OBJECTIVE
Microsomal epoxide
hydrolase is an important enzyme involved in the metabolism of
endogenous and exogenous toxicants. Polymorphic variants of the human
epoxide hydrolase gene vary in enzyme activity. We determined whether
genetic variability in the gene encoding for microsomal epoxide
hydrolase contributes to individual differences in susceptibility to
the development of pre-eclampsia with or without the syndrome of
Haemolysis, Elevated Liver enzymes, and Low Platelets (HELLP).
METHODSA total of 183 non-pregnant women with a history of pre-eclampsia, 96 of whom had
concurrently developed the HELLP syndrome, and 151 healthy female
controls were genotyped for the 113Tyr
His polymorphism in exon 3 and
the 139HisArg polymorphism in exon 4 of the epoxide hydrolase gene
by a polymerase chain reaction-restriction fragment length polymorphism
assay. Chi-square analysis was used for statistical evaluation of
differences in polymorphic rates.
RESULTSIn pre-eclampsia a
higher frequency (29%) of the high activity genotype Tyr113 Tyr113 in
exon 3 was found as compared to controls (16%, OR 2.0, 95% CI
1.2-3.7). There was no difference between groups for the 139HisArg
polymorphism. In women with a history of pre-eclampsia, no difference
in epoxide hydrolase genotypes was found between women who either did
or did not develop the HELLP syndrome. In addition, a significant
association was found between predicted EPHX activity and
pre-eclampsia.
CONCLUSIONSWomen with the high
activity genotype in exon 3, which could reflect differences in
metabolic activation of endogenous or exogenous toxic compounds, may
have enhanced susceptibility to pre-eclampsia. However, polymorphisms
in the epoxide hydrolase gene do not seem to influence the risk for
concurrent development of the HELLP syndrome.
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