Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and Coagulation Factor XIII Val34Leu Polymorphism: Impaired Fibrinolysis and Early Pregnancy Loss

Abstract

Background: A successful outcome of pregnancy depends on proper placental formation. In the very beginning of this process, trophoblast invasion and fibrin deposition into the wall of the decidual veins play an important part. Two polymorphisms, coagulation factor XIII (FXIII) Val34Leu and plasminogen activator inhibitor 1 (PAI-1) 4G/5G, interfere with fibrin cross-linking and regulation of fibrinolysis and may therefore contribute to early pregnancy loss. Methods: We enrolled 49 unrelated Caucasian women with a history of two consecutive or three to six nonconsecutive early pregnancy losses and 48 unrelated parous healthy controls without a history of pregnancy loss and evaluated them for the following genetic variants: the factor V Leiden and prothrombin G20210A gene mutations, the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and the PAI-1 4G/5G and FXIII Val34Leu polymorphisms. Results: For the isolated occurrence of PAI-1 4G/5G or FXIII Val34Leu, we found no statistically significant difference between cases and controls. For homozygosity of either or compound carrier status of both mutations, the overall relative risk for early pregnancy loss was significantly increased (odds ratio ‫؍‬ 2.4; 95% con-

Polymorphisms of Plasminogen Activator Inhibitor-1 4G/5G, Coagulation Factor XIII Val34Leu and Angiotensin Converting Enzyme I/D Impact on Recurrent Implantation Failure

“…This coincides with the results of a recent study which pointed out that heterozygosity and, to a slightly larger extent, homozygosity for FXIII Val34Leu polymorphism might be considered as risk factors for RPL [21]. In addition, FXIII Val34Leu polymorphism has been reported to carry an elevated overall risk for RPL in women homozygous for the FXIII 34Leu as well as in compound carriers of the FXIII 34Leu [12].…”

“…FXIII Val34Leu polymorphism in exon 2 of the FXIII gene is correlated with earlier cross-linking, a finer fibrin meshwork formation, and lower susceptibility to fibrinolysis [11]. This polymorphism has been reported to carry an elevated overall risk for RPL in women homozygous for the FXIII 34Leu [12].…”

Toward optimal set of single nucleotide polymorphism investigation before IVF

“…Although there are some data about influence absence or disputed impact of the 4G allele in the female reproductive system [27], the most research suggests undoubted negative impact of the 4G allele for habitual miscarriage, IVF failure and polycystic ovary syndrome [15,[28][29][30]. Present data confirm this point of view.…”

“…SNP V34L 103 G4T is closely associated with the risk of thrombosis: it is repeatedly shown a protective effect of T allele against the development of cardiovascular disease [70]. On the influence pathologic alleles of this polymorphism on the risk of early miscarriage reported Dossenbach-Glaninger et al [29]. There are also the data, the simultaneous and the same authors, describing no effect of genotype on this SNP for venous thrombosis [71].…”

“…ACE protein functionality and features of its expression, associated with the presence of Alu-sequences in the intron, are devoted to a great number of publications [55,56,[60][61][62]. Virtually all studies agree that the presence of variant D (Del), lack of Alu-sequences in the intron of the ACE gene, is associated with atherosclerotic, cardiovascular disorders and the risk of pregnancy violation [29,61,62]. At the molecular level, Alu insertion reduces the gene expression level that is displayed as s decrease in the level of ACE protein in the blood and more precise regulation of blood pressure without pronounced spikes as a consequence.…”