Genetic polymorphism of catechol-O-methyltransferase and cytochrome P450c17alpha in preeclampsia.

摘要

OBJECTIVE: Catechol-O-methyltransferase (COMT) and cytochrome P450c17alpha (CYP17A1) are key enzymes involved in the metabolism of steroid hormones; genetic polymorphisms in these genes affect enzyme activity. Recently, functional polymorphisms in the COMT and CYP17A1 genes have been suggested as a susceptible marker for intrauterine fetal growth restriction, a typical complication of preeclampsia. Moreover, a close association between COMT and preeclampsia was reported. We therefore investigated the relationships between COMT and CYP17A1 polymorphisms and the risk of preeclampsia. METHODS: A total of 164 preeclamptic women and 182 normotensive women were enrolled. COMT (Val158Met) and CYP17A1 (-34T/C) polymorphisms were genotyped by quantitative fluorescent-polymerase chain reaction. Multiple logistic regression analysis was used to estimate the risks of preeclampsia according to genotypes. RESULTS: The adjusted odds ratios (adjOR) for the risks of preeclampsia, severe preeclampsia and preeclampsia for small-for-gestational-age (SGA) infants were 1.97 [95% confidence interval (CI): 1.02-3.83], 3.29 (95% CI: 1.60-6.77), and 4.05 (95% CI: 1.78-9.22), respectively, in women homozygous for the variant COMT allele. No significant differences were observed between the two groups with respect to CYP17A1 polymorphisms, indicating that variants of this gene have no effects on preeclampsia. The highest risks of preeclampsia were found among women with homozygous variant genotypes of both genes [adjOR (95% CI): 4.58 (1.92-22.81)]. Moreover, the adjOR for preeclamptic complications in those women was 5.09 (95% CI: 1.93-27.88) for severe preeclampsia and 15.65 (95% CI: 3.19-76.82) for SGA preeclampsia. CONCLUSION: These findings suggest that homozygosity for the variant allele of the maternal COMT gene may increase susceptibility to preeclampsia.