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Thromb Haemost 2012; 108(04): 693-700
DOI: 10.1160/TH12-03-0177
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Elvira M. Guerra-Shinohara
1   Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, S P, Brasil
,
Juliano Felix Bertinato
1   Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, S P, Brasil
,
Carolina Tosin Bueno
1   Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, S P, Brasil
,
Kelma Cordeiro da Silva
1   Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, S P, Brasil
,
Mário Henrique Burlacchini de Carvalho
2   Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina, Universidade de São Paulo, S P, Brasil
,
Rossana Pulcineli Vieira Francisco
2   Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina, Universidade de São Paulo, S P, Brasil
,
Marcelo Zugaib
2   Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina, Universidade de São Paulo, S P, Brasil
,
Alvaro Cerda
1   Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, S P, Brasil
,
Vânia Maris Morelli
3   Disciplina de Hematologia e Hemoterapia, Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, S P, Brasil
› Author Affiliations
Further Information

Publication History

Received: 21 March 2012

Accepted after major revision: 28 July 2012

Publication Date:
29 November 2017 (online)

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Summary

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.

Keywords

Antithrombin - protein C - thrombomodulin - tissue factor pathway inhibitor - gene polymorphisms - recurrent pregnancy loss - miscarriages
 

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