Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Author(s)

Guerra-Shinohara, Elvira M. ^[1] ; Bertinato, Juliano Felix ^[1] ; Bueno, Carolina Tosin ^[1] ; da Silva, Kelma Cordeiro ^[1] ; Burlacchini de Carvalho, Mario Henrique ^[2] ; Vieira Francisco, Rossana Pulcineli ^[2] ; Zugaib, Marcelo ^[2] ; Cerda, Alvaro ^[1] ; Morelli, Vania Maris ^[3]

Affiliation

^[1] Univ Sao Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Obstet & Ginecol, Fac Med, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Oncol Clin & Expt, Disciplina Hematol & Hemoterapia, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: THROMBOSIS AND HAEMOSTASIS; v. 108, n. 4, p. 693-700, OCT 2012.
• Web of Science Citations: 5

Abstract

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A > G, PROC 2405C > T, THBD 1418C > T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio {[}OR]: 1.77, 95% confidence interval {[}CI]: 1.05-3.00, p=0.034) while women carrying the TFPI-287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26 - 0.83, p=0.009). The TCC haplotype for TFPI T-33C/TFPI T-287C/TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23 - 0.90, p=0.025). In conclusion, our data indicate that SERPINC1 786G > A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings. (AU)