Polymorphisms in Antitrombin (SERPINC1) and Tissue Factor Pathway Inhibitor (TFPI) Genes Are Associated with Recurrent Pregnancy Loss

Abstract

Abstract 711 Background:Recurrent pregnancy loss (RPL) is a multifactorial condition. The effects of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) gene polymorphisms in the risk of having RPL are unknown. Aims:To determine the effects of SERPINC1, PROC, THBD and TFPI gene polymorphisms in the risk of having RPL. Methods:One hundred and fifteen non-pregnant women with three consecutive losses prior to 20 weeks of pregnancy without carrying a fetus to viability (primary RPL) and 253 healthy fertile non-pregnant women who had at least two children and no known pregnancy losses were studied. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292 and rs8176592) gene polymorphisms were detected respectively by Real Time PCR. Results:No difference was observed among the genotypes frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T and TFPI T-33C polymorphisms in two groups (Table 1, P>0.05). However, the carriers of 140T allele (CT + TT genotypes) for SERPINC1 C+140T polymorphism had 1.73 (95% CI: 1.00 – 2.99) times risk of having RPL. Furthermore, the carriers of TC + CC genotypes for TFPI T-287C polymorphism had a protection effect of having RPL (OR: 0.48, 95% CI 0.27– 0.86). Conclusions:The variant of SERPINC1 C+140T polymorphism is associated with higher risk of having RPL while the variant of TFPI T-287C polymorphism is associated with a protection effect.Table 1 –Genotypes distributions of investigated SNPsPolymorphismSNP IDChrChr positionGenotypesRPL groupControl groupOR (CI 95%)P valorPROC 2418A>Grs17998092128175875AA37 (32.5)88 (34.8)1.00AG + GG77 (67.5)165 (65.2)1.11 (0.69–1.78)0.663PROC 2405C>Trs17998082128175862CC42 (36.8)87 (34.4)1.00CT + TT72 (63.2)166 (65.6)0.90 (0.57–1.42)0.649SERPINC1 C+140Trs22275891173886216CC86 (75.4)213 (84.2)1.00CT + TT28 (24.6)40 (15.8)1.73 (1.00–2.99)0.047THBD c.1418C>Trs10425792023028724CC87 (76.3)195 (77.1)1.00CT + TT27 (23.7)58 (22.9)1.04 (0.62–1.76)0.873TFPI T-287Crs109312922188419479TT97 (85.1)185 (73.1)1.00TC + CC17 (14.9)68 (26.9)0.48 (0.27–0.86)0.013TFPI T-33Crs81765922188332692TT51 (44.7)114 (45.1)1.00TC + CC63 (55.3)139 (54.9)1.01 (0.65–1.58)0.954Chr: chromosome; SNP: single nucleotide polymorphisms; RPL: recurrent pregnancy loss.The data are absolute (relative) frequencies.Financing: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2007/57605-0) Disclosures:No relevant conflicts of interest to declare.