Zusterzeel P L, Peters W H, Visser W, Hermsen K J, Roelofs H M, Steegers E A
Department of Obstetrics and Gynaecology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
J Med Genet. 2001 Apr;38(4):234-7. doi: 10.1136/jmg.38.4.234.
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).
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 female controls were genotyped for the 113Tyr-->His polymorphism in exon 3 and 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.
In 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 139His-->Arg 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.
Women 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.
微粒体环氧化物水解酶是一种参与内源性和外源性毒物代谢的重要酶。人类环氧化物水解酶基因的多态性变体在酶活性方面存在差异。我们确定了微粒体环氧化物水解酶编码基因的遗传变异性是否会导致患先兆子痫（无论是否伴有溶血、肝酶升高和血小板减少综合征即HELLP综合征）易感性的个体差异。
对总共183名有先兆子痫病史的未孕女性（其中96名同时并发HELLP综合征）以及151名健康女性对照，通过聚合酶链反应-限制性片段长度多态性分析，对环氧化物水解酶基因外显子3中的113Tyr→His多态性和外显子4中的139His→Arg多态性进行基因分型。采用卡方分析对多态性频率差异进行统计学评估。
与对照组（16%，比值比2.0，95%可信区间1.2 - 3.7）相比，先兆子痫患者中外显子3中高活性基因型Tyr113 Tyr113的频率更高（29%）。139His→Arg多态性在各组之间没有差异。在有先兆子痫病史的女性中，并发或未并发HELLP综合征的女性之间环氧化物水解酶基因型没有差异。此外，还发现预测的EPHX活性与先兆子痫之间存在显著关联。
外显子3中具有高活性基因型的女性，这可能反映了内源性或外源性有毒化合物代谢激活的差异，可能对先兆子痫的易感性增强。然而，环氧化物水解酶基因的多态性似乎并不影响并发HELLP综合征的风险。
