Thrombophilic Mutations and Folate Gene Polymorphisms and Plasminogen Activator Inhibitor-1 in Russian Women with Unexplained Recurrent Early Spontaneous Abortion

Aims: To assess the association between FVL G1691A, FII G20210A, MTHFR A1298C, C677T and PAI-1 5G/675/4G gene polymorphisms among women with unexplained recurrent early spontaneous abortion (URESA)
Materials and Methods: This study included two groups of Russian women: 50 currently non-pregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (URESA group), and 50 currently non-pregnant women with a history of having given birth to at least one live baby and without a history of spontaneous abortion, prematurity, stillbirth, eclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time (PCR-RT). We have analyzed the frequencies, χ2 test, odds ratio (OR) and its 95% confidence interval (CI), Hardy-Weinberg equilibrium.
Results: Significant association between heterozygotes genotype FVL 1691G/A and URESA was found (OR=3.1). Heterozygous genotype FII20210G/A was associated mainly with recurrent spontaneous abortions (4% vs 0%). The PAI-1 5G/4G genotype was significantly associated with URESA (OR=2.3). Heterozygotes with MTHFR 677C/T genotype had high risk of early recurrent pregnancy loss (OR=4.6). Heterozygotes with MTHFR 1298A/C genotype showed low association with pregnancy loss (OR=1.2). We did not observe increased risk of early pregnancy loss in mutant homozygotes with MTHFR 677C/C and 1298C/C genotypes (OR=1.0). The presence of the PAI-1 gene 5G/4G genotype together with the MTHFR 677C/T or MTHFR 1298A/C or FVL 1691G/A genotypes was found to be a risk factor for URESA (OR=4.5; OR=2.3, respectively). Combined PAI-1 5G/4G// FVL 1691G/A genotypes was detected only in patients (2% vs 0%). Women carrying combined PAI-1 5G/4G//MTHFR 677C/T//MTHFR 1298A/C genotypes had an increased frequency of recurrent early spontaneous abortion (OR=1.4).
Conclusion: The genetic polymorphisms of FVL 1691G/A, FII 20210G/A, MTHFR 677C/T, MTHFR 1298A/C, and PAI-1 4G/4G, and the PAI-1 5G/4G genotypes are associated with URESA. The patients carrying combined heterozygous genotypes PAI-1 5G/4G//MTHFR 677C/T or PAI-1 5G/4G//MTHFR 1298A/C or PAI-1 5G/4G//FVL 1691G/A or PAI-1 5G/4G//MTHFR 677C/T//MTHFR 1298A/C have higher risks of URESA. These results might indicate a genetic influence on pathogenesis of URESA.