Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss.
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.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, SP, Brasil. emguerra@usp.br
Elvira M
EM
Guerra-Shinohara
Juliano Felix
JF
Bertinato
Carolina
C
Tosin Bueno
Kelma
K
Cordeiro da Silva
Mário Henrique
MH
Burlacchini de Carvalho
Rossana
R
Pulcineli Vieira Francisco
Marcelo
M
Zugaib
Alvaro
A
Cerda
Vânia Maris
VM
Morelli
D000026:Abortion, Habitual / Q000097:blood / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000990:Antithrombin III / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008074:Lipoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011486:Protein C / Q000235:genetics*; D018180:Thrombomodulin / Q000235:genetics*
D008074:Lipoproteins; D011486:Protein C; C542513:SERPINC1 protein, human; C546931:THBD protein, human; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III