Molecular Human Reproduction, Vol. 9, No. 11, 725-728,
November 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss
Submitted on May 27, 2003; resubmitted on July 15, 2003. accepted on July 28, 2003
1 Department of Public Heath and 2 Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan
3 To whom correspondence should be addressed. e-mail: fsata{at}med.hokudai.ac.jp
The CYP17 gene encodes the enzyme cytochrome P450c17
, which mediates both 17-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 TC 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.
Key words: CYP17/estrogen/genetic polymorphism/molecular epidemiology/recurrent pregnancy loss
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