title: Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease.
abstract: Increased circulating levels of type 1 plasminogen activator inhibitor (PAI-1) have been associated with coronary artery disease (CAD). However, genetic and environmental determinants of PAI-1 expression are only partially understood. The levels of PAI-1 have been found to relate to 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene. The 4G allele in this polymorphism has been associated with higher levels of plasma PAI-1 activity, but despite the strong correlation between PAI-1 activity and antigen, no association has been found between PAI-1 antigen levels and the PAI-1 promoter 4G/5G genotype. The aim of the present study was to analyze the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels in post-menopause women with coronary disease in comparison with healthy women in pre and postmenopausal status, and the influence of this genotype on variations in PAI-1 levels after hormone replacement therapy (HRT). No differences between 4G/5G allele distribution in the groups studied were observed. The group of postmenopausal women with CAD showed significantly increased PAI-1 antigen and activity levels in comparison with the control groups, and the levels of PAI-1 correlated with the 4G/5G genotype. A multivariate analysis revealed that in the CAD group there was a high correlation between 4G allele dosage and PAI-1 antigen levels, which were also influenced by the triglyceride levels but not by estrogen or glucose levels. After hormone replacement therapy the decrease in PAI-1 levels was correlated with the 4G allele dosage. We conclude that in the group of postmenopausal women with CAD the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels is more evident than in the control groups, and that the decrease in PAI-1 levels after HRT in CAD women correlates with the 4G allele dosage.
authors.affiliation: University Hospital La Fe, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Grancha
authors.forename: A
authors.initials: A
authors.lastname: Estellés
authors.forename: G
authors.initials: G
authors.lastname: Tormo
authors.forename: C
authors.initials: C
authors.lastname: Falco
authors.forename: J
authors.initials: J
authors.lastname: Gilabert
authors.forename: F
authors.initials: F
authors.lastname: España
authors.forename: A
authors.initials: A
authors.lastname: Cano
authors.forename: R
authors.initials: R
authors.lastname: Segui
authors.forename: J
authors.initials: J
authors.lastname: Aznar
mesh_terms: D000941:Antigens / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D004967:Estrogens / Q000097:blood; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D017698:Postmenopause / Q000097:blood*; D011401:Promoter Regions, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D000941:Antigens; D001786:Blood Glucose; D004967:Estrogens; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D002784:Cholesterol