Premium
Plasminogen Activator Inhibitor 1 4G/5G and −844G/A Variants in Idiopathic Recurrent Pregnancy Loss
Author(s) -
Magdoud Kalthoum,
Herbepin Viviana G.,
Touraine Renaud,
Almawi Wassim Y.,
Mahjoub Touhami
Publication year - 2013
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12116
Subject(s) - single nucleotide polymorphism , genotyping , haplotype , plasminogen activator inhibitor 1 , fibrinolysis , biology , genotype , plasminogen activator , pregnancy , snp , allele , case control study , genetics , medicine , allele frequency , endocrinology , gene
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 .