Introduction: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. Aim: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. Results: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). Conclusions: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

Due to inconsistent results of APOE variants in the survival of pregnancy we investigated the potential relationship of APOE rs7412 and rs429358 with pregnancy loss (PL) in Bosnian women. We enrolled 154 women with PL. The minimum week of miscarriage was 6, while the maximum was 28. As a control group, an equal number of mothers with at least one live-born child was included. All women were recruited from the Institution of Health Protection of Women and Motherhood in Sarajevo, Bosnia and Herzegovina. Genotyping was performed by real- time PCR at the Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University. The prevalence of genotypes E2/E3, E2/E4, E3/E3, E3/E4, E4/E4 in the group with and without PL were: 14.3 %, 1.3 %, 70.8 %, 12.3 %, 1.3 %, and 13.6 %, 1.3 %, 70.1 %, 14.3 %, 0.7 %, respectively. The frequency of the E4/E4 genotype in women with 1-2 and 3-4 PL compared to women without PL did not differ significantly between those three groups (P value = 0.0712). The frequencies of alleles ԑ2, ԑ3, ԑ4 in the group with and without PL were: 6.8 %, 85.1 %, 8.1 % and 7.5 %, 84.1 %, 8.4 %, respectively, and did not differ significantly. We conclude that our study does not confirm rs7412 and rs429358 as a potential risk factor for PL in the studied group. To elucidate the relationship between PL and variants of the APOE gene, studies with a larger sample size and placental histomorphology and genetic diagnosis are required.

The relationship between genetic risk factors of thrombophilia and pregnancy loss (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Although, the frequencies of these polymorphisms were reported in different populations, such studies have not yet been performed in Bosnian population. In this study, we determined the prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133) polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (±5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age 31.4 (±6.7) years] with at least one live-born child were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was significantly higher in women with venous thrombosis (VT) compared to women without VT (p = 0.047 and p = 0.001, respectively). There was no significant difference in the distribution of MTHFR genotypes and alleles between these two groups. In addition, we observed no significant differences in the genotype and allele frequencies between the group with PL and control group, for all investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2), and 677T (MTHFR) reported in this study are consistent with the data obtained for other European countries, however, we were not able to confirm the association between the three polymorphisms and PL in Bosnian women.