A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia

Objective-Microsomal epoxide hydrolase is an important enzyme involved in t he metabolism of endogenous and exogenous toxicants. Polymorphic variants o f the human epoxide hydrolase gene vary in enzyme activity. We determined w hether genetic variability in the gene encoding for microsomal epoxide hydr olase contributes to individual differences in susceptibility to the develo pment of pre-eclampsia with or without the syndrome of Haemolysis, Elevated Liver enzymes, and Low Platelets (HELLP). Methods-A total of 183 non-pregnant women with a history of pre-eclampsia, 96 of whom had concurrently developed the HELLP syndrome, and 151 healthy f emale controls were genotyped for the 113Tyr-->His polymorphism in exon 3 a nd the 139His-->Arg 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. Results-In pre-eclampsia a higher frequency (29%) of the high activity geno type 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 139His--> Arg polymorphism. In women with a history of pre-eclampsia, no difference i n 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. Conclusions-Women with the high activity genotype in exon 3, which could re flect differences in metabolic activation of endogenous or exogenous toxic compounds, may have enhanced susceptibility to pre-eclampsia. However, poly morphisms in the epoxide hydrolase gene do not seem to influence the risk f or concurrent development of the HELLP syndrome.