Polymorphisms in the clotting Factors II, V and XI Genes and Risk of Recurrent Pregnancy Loss in Gaza Strip

Abstract

Background: Recurrent miscarriage is defined as the occurrence of three or more consecutive pregnancy losses during the first trimester, and accounts for about 1-3% of clinically recognized pregnancy losses. Despite extensive research to explain the causative effects of recurrent pregnancy loss (RPL), about 50%-60% of RPLs are still idiopathic. Despite the increasing prospective studies with sufficient power related to the association between various thrombophilias and RPL, controversy still remains regarding screening for thrombophilia in women with RPL. Objective: To investigate the association between recurrent pregnancy loss (RPL) and common polymorphisms in factor-V G1691A, factor-V H1299R (A4070G), factor-V Y1702C (A5279G), factor-II G20210A, and factor-XI rs3756008 (A>T) genes in Gaza strip- Palestine. Methods: This study is an association study with a case-control design. Using molecular biological techniques, the factor-V G1691A, factor-V H1299R (A4070G), factor-V Y1702C (A5279G), factor-II G20210A, and factor-XI rs3756008 (A>T) polymorphisms were determined for 200 women who had at least three consecutive abortions and 200 controls without a previous history of abortion. Results: The factor V: G1691A is associated with and may represent a risk factor for RPL in our population. The A-allele seems to significantly double the risk for RPL (OR = 2.06; P = 0.0093). Factor V: A4070G is also associated with RPL in our population with the G-allele increasing the RPL risk more than three times (OR = 3.14; P = 0.003). Factor V: A5279G was not significantly different between RPL patients and controls (P-value = 0.140). Factor II: G20210A also did not significantly differ between RPL patients and controls (P-value = 0.096). Factor XI: rs3756008 (A>T) allele frequencies showed that there is no significant difference between the RPL patients and the controls (P-value = 0.15). After excluding the three samples in which both G1691A and A4070G polymorphisms coexisted, the A4070G minor allele remained as a risk factor for RPL with an odds ratio of (OR = 2.34; P = 0.0003), implicating that A4070G represent an independent risk factor for RPL. Conclusion: The study showed that there is significant associations between factor V: G1691A (R506Q; rs6025) and H1299R (R2) polymorphisms and RPL. No significant association was observed between Y1702C (rs118203907); factor II G20210A (rs1799963), and factor XI rs3756008 (A>T) polymorphisms and RPL.