title: Plasminogen activator inhibitor 1 4G/5G and -844G/A variants in idiopathic recurrent pregnancy loss.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  4G/5G, but not -844G/A, PAI-1 variant is associated with an increased risk of RPL.
authors.affiliation: Research unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Kalthoum55@yahoo.fr
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Magdoud
authors.forename: Viviana G
authors.initials: VG
authors.lastname: Herbepin
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1
keywords: plasminogen activator inhibitor-1; polymorphism; recurrent miscarriage