Plasminogen Activator Inhibitor 1 4G/5G and −844G/A Variants in Idiopathic Recurrent Pregnancy Loss

Problem Plasminogen activator inhibitor type 1 ( PAI ‐1) regulates fibrinolysis, and the common promoter region variants −675G/A (4G/5G) and −844G/A are associated with increased thrombotic risk. Despite evidence linking altered fibrinolysis with adverse pregnancy events, including idiopathic recurrent pregnancy loss ( RPL ), the contribution of PAI ‐1 variants to RPL risk remains controversial. We investigated the association between the PAI ‐1 −844G/A and 4G/5G (−675G/A) variants with altered risk of RPL . Method of study This was a case–control study involving 304 women with confirmed RPL and 371 age‐ and ethnically matched control women. PAI ‐1 genotyping was performed by PCR single‐specific primer −675 (G/A) and real‐time PCR (−844G/A) analysis. Results Minor allele frequency ( MAF ) of 4G/5G ( P  <   0.001), but not −844G/A ( P  =   0.507), was higher in RPL cases. PAI ‐1 4G/5G single‐nucleotide polymorphism ( SNP ) was significantly associated with RPL under additive, dominant, and recessive genetic models; no association of −844G/A with RPL was seen irrespective of the genetic model tested. Taking common −844G/5G haplotype as reference ( OR  = 1.00), multivariate analysis confirmed the association of 4G‐containing −844A/4G ( P  <   0.001) and −844G/4G ( P  =   0.011) haplotypes with increased RPL risk. Conclusion 4G/5G, but not −844G/A, PAI ‐1 variant is associated with an increased risk of RPL .