Background: Recurrent pregnancy loss (RPL) affects up to 5% of pregnancies, but with no consensus on the definition. Inherited thrombophilia has been postulated as a risk factor for RPL. The aim of this study was to investigate the association of RPL with polymorphisms of five genes that influent the coagulation and fibrinolysis.
Methods: This study was conducted on total of 224 women, 129 women with ≥2 early RPL or ≥1 late pregnancy loss, 95 women with at least two normal life births and no history of pregnancy loss. Five gene polymorphisms F2 20 210G>A (rs1799963), F5 1691G>A (rs6025), MTHFR 677C>T (rs1801133), SERPINE1 -675 4G/5G (rs1799762) and ACE I/D (rs1799752) were genotyped by PCR-based methods.
Results: A significant relationship was found between SERPINE1 4G/4G and ACE D/D polymorphisms and RPL (p<0.001 both, OR 2.91 and 3.02, respectively). In contrast, no association was found between F2 20 210G>A, F5 1691G>A and MTHFR 677C>T polymorphisms and risk for RPL. A combination of hypofibrinolytic homozygotes SERPINE1 4G/4G+ACE D/D was observed as a highly associated with RPL (Cochran-Armitage test, p<0.001), and their strong independent association with RPL risk was confirmed by logistic regression analysis (both p values <0.001, OR 3.35 and 3.43, respectively).
Conclusion: Our data have demonstrated that SERPINE1 and ACE gene polymorphisms, individually or in combination, appear to be a significant risk for RPL. This data may be useful in adding to the knowledge on inherited thrombophilia as an important contributor to RPL pathogenesis.
Keywords: blood coagulation; fibrinolysis; genetics; pregnancy; thrombophilia.
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