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58 THE PREVALENCE OF 4G5G POLYMORPHISM OF THE PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) GENE IN POLYCYSTIC OVARIAN SYNDROME AND ITS ASSOCIATION WITH PLASMINOGEN ACTIVATOR INHIBITOR ACTIVITY LEVELS
  1. C. J. Glueck,
  2. L. Sieve,
  3. M. Salehi,
  4. P. Wang
  1. Jewish Hospital, Cincinnati

Abstract

We assessed the mutant 4G allele of the plasminogen activator inhibitor-1 (PAI-1) gene in women with polycystic ovary syndrome (PCOS) and its relationship to hypofibrinolytic plasminogen activator inhibitor activity (PAI-Fx), an independent determinant of miscarriage in PCOS. We studied 913 women with PCOS who met the 2003 ESHRE/ASRM diagnostic consensus criteria and 126 healthy normal female controls. Of the 913 PCOS women, 78% had 4G4G or 4G5G genotypes vs 69% of controls (χ2 = 4.98, p = .026). The 4G allele frequency was 53% in PCOS women vs 46% in controls (χ2 = 4.06, p = .044). PCOS and normal women were both in Hardy-Weinberg equilibrium for the PAI-1 genotype distribution. By stepwise multiple regression, positive independent determinants of PAI-Fx included BMI (partial R2 = 10.8%, p<.0001), serum insulin (partial R2 = 2.7%, p<.0001), 4G4G-4G5G genotype (partial R2 = 1%, p = .0022), and triglyceride (partial R2 = 1%, p<.002); PAI-Fx was inversely associated with age (partial R2 = .5%, p = .02). Of the 913 women, 409 had previous pregnancies. By logistic regression with the dependent variable being live birth pregnancies only (n = 191), or miscarriages only (n= 69), and explanatory variables PAI-1 genotype, PAI-Fx, insulin, BMI, and triglyceride, PAI-Fx was positively associated with miscarriage, p = .017. The 4G polymorphism of the PAI-1 gene is more common in PCOS than normal women and contributes to hypofibrinolytic-miscarriage-promoting PAI-Fx levels in concert with hyperinsulinemia and hypertriglyceridemia. The 4G polymorphism of the PAI-1 gene and high PAI-Fx are markers for PCOS and its endocrine-metabolic-reproductive correlates.

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