Sata F, Yamada H, Yamada A, Kato E H, Kataoka S, Saijo Y, Kondo T, Tamaki J, Minakami H, Kishi R
Department of Public Heath, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Mol Hum Reprod. 2003 Nov;9(11):725-8. doi: 10.1093/molehr/gag089.
The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T-->C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T-->C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.
CYP17基因编码细胞色素P450c17α酶，该酶在类固醇生物合成途径中介导17α-羟化酶和17,20-裂解酶活性。CYP17基因5'启动子区域存在T→C多态性。为了研究复发性流产（RPL）与CYP17基因多态性之间的关联，对117例RPL患者和164例对照进行了病例对照研究。采用外周血淋巴细胞DNA，通过聚合酶链反应/限制性片段长度多态性方法研究该多态性。变异等位基因（A2）中的T→C转换产生了限制性酶MspA1的新识别位点，从而可以区分野生型等位基因（A1）和A2。携带CYP17基因A2等位基因的女性发生RPL的风险增加[A1/A1基因型（参照）；A1/A2基因型：优势比（OR）为1.68；95%置信区间（CI）为0.94 - 3.01；A2/A2基因型：OR为2.37；95%CI为1.16 - 4.83；P趋势为0.016]。此外，原发性RPL风险增加也有类似趋势[A1/A1基因型（参照）；A1/A2基因型：OR为2.14；95%CI为1.14 - 4.01；A2/A2基因型：OR为2.50；95%CI为1.16 - 5.41；P趋势为0.015]。这些结果表明，携带CYP17基因A2变异体可能因基因剂量效应而使RPL风险增加。
