Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, KwanDong University College of Medicine, Chung-gu, Seoul, Korea.
Pharmacogenet Genomics. 2010 Oct;20(10):605-10. doi: 10.1097/FPC.0b013e32833df033.
Catechol-O-methyltransferase (COMT) and cytochrome P450c17α (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.
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.
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.
These findings suggest that homozygosity for the variant allele of the maternal COMT gene may increase susceptibility to preeclampsia.
儿茶酚氧位甲基转移酶（COMT）和细胞色素 P450c17α（CYP17A1）是参与类固醇激素代谢的关键酶；这些基因的遗传多态性影响酶活性。最近，COMT 和 CYP17A1 基因的功能多态性被认为是子痫前期典型并发症宫内胎儿生长受限的易感标志物。此外，已有报道称 COMT 与子痫前期密切相关。因此，我们研究了 COMT 和 CYP17A1 多态性与子痫前期风险之间的关系。
共纳入 164 例子痫前期妇女和 182 例正常血压妇女。采用荧光定量聚合酶链反应法检测 COMT（Val158Met）和 CYP17A1（-34T/C）多态性。采用多因素 logistic 回归分析估计基因型与子痫前期、重度子痫前期及子痫前期合并胎儿生长受限（SGA）的风险比（adjOR）。
COMT 变异等位基因纯合子的子痫前期、重度子痫前期和子痫前期合并 SGA 婴儿的调整后比值比（adjOR）分别为 1.97（95%可信区间[CI]：1.02-3.83）、3.29（95% CI：1.60-6.77）和 4.05（95% CI：1.78-9.22）。CYP17A1 多态性在两组间无显著差异，提示该基因的变异对子痫前期无影响。两个基因变异等位基因纯合子的妇女发生子痫前期的风险最高[adjOR（95% CI）：4.58（1.92-22.81）]。此外，这些妇女子痫前期并发症的 adjOR 为重度子痫前期 5.09（95% CI：1.93-27.88），SGA 子痫前期 15.65（95% CI：3.19-76.82）。
这些发现表明，母体 COMT 基因变异等位基因纯合可能增加子痫前期的易感性。
