Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

Abstract

SummaryBackgroundRecurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls.MethodsThe study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays.ResultsOur results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15–6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11–17.46, P=0.044).ConclusionsThis is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

“…32 39 86 In 26 studies (37%) the controls were matched to the cases. 22 23 25 28 29 30 34 38 39 45 46 52 54 58 60 61 63 65 66 68 70 71 72 75 87 91…”

“…The association between PAI-1 genotype and pregnancy loss was investigated in 45 studies. 23 27 28 29 30 31 37 38 39 40 41 42 43 44 46 48 50 51 52 53 55 56 57 58 59 60 62 63 64 65 66 68 76 77 78 79 80 81 82 83 84 88 89 90 91 Pregnancy loss was described as miscarriage, abortion, fetal loss, or intrauterine fetal death. The definition differed across studies according to gestational week and number of pregnancy losses.…”

“…Table 2 shows extracted data from the 11 studies investigating the association between PAI-1 levels in pregnant women and placenta-mediated pregnancy complications. Of the 71 included studies, 15 were rated good, 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 39 were rated fair, 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 and 17 were rated poor. 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92…”

“…Twenty-one studies investigated cases with preeclampsia, 22 24 34 35 36 45 47 49 54 61 67 69 70 71 72 73 74 75 86 87 92 45 studies investigated cases with pregnancy loss described as pregnancy loss, 27 29 31 39 50 51 52 59 60 64 66 68 81 90 91 miscarriage, 23 28 30 38 40 41 42 44 53 55 56 57 58 62 65 76 78 79 88 abortion, 37 43 48 63 77 83 89 fetal loss, 46 80 82 or intrauterine fetal death. 84 One study investigated cases delivering still birth, 33 one study investigated cases delivering newborns meeting the criteria for intrauterine growth restrictions, 26 and three studies investigated cases with various adverse pregnancy outcomes.…”

“…In 32 of the 59 studies investigating PAI-1 4G/5G polymorphism and placenta-mediated pregnancy complications no association between PAI-1 4G/5G polymorphism and placenta-mediated pregnancy complications was identified. 22 23 24 26 28 30 31 32 38 40 42 43 44 45 46 49 51 52 53 56 57 58 61 65 77 80 81 83 84 85 87 88…”