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Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease.
Thromb Haemost. 1999 Apr; 81(4):516-21.TH

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+Show Affiliations

Grancha S
University Hospital La Fe, Valencia, Spain.
Estellés A
No affiliation info available
Tormo G
No affiliation info available
Falco C
No affiliation info available
Gilabert J
No affiliation info available
España F
No affiliation info available
Cano A
No affiliation info available
Segui R
No affiliation info available
Aznar J
No affiliation info available

MeSH

AntigensBlood GlucoseCholesterolCoronary DiseaseEstrogensFemaleGenotypeHormone Replacement TherapyHumansMiddle AgedMyocardial InfarctionPlasminogen Activator Inhibitor 1PostmenopausePromoter Regions, GeneticTriglycerides

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10235431

Citation

Grancha, S, et al. "Plasminogen Activator Inhibitor-1 (PAI-1) Promoter 4G/5G Genotype and Increased PAI-1 Circulating Levels in Postmenopausal Women With Coronary Artery Disease." Thrombosis and Haemostasis, vol. 81, no. 4, 1999, pp. 516-21.
Grancha S, Estellés A, Tormo G, et al. Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease. Thromb Haemost. 1999;81(4):516-21.
Grancha, S., Estellés, A., Tormo, G., Falco, C., Gilabert, J., España, F., Cano, A., Segui, R., & Aznar, J. (1999). Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease. Thrombosis and Haemostasis, 81(4), 516-21.
Grancha S, et al. Plasminogen Activator Inhibitor-1 (PAI-1) Promoter 4G/5G Genotype and Increased PAI-1 Circulating Levels in Postmenopausal Women With Coronary Artery Disease. Thromb Haemost. 1999;81(4):516-21. PubMed PMID: 10235431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease. AU - Grancha,S, AU - Estellés,A, AU - Tormo,G, AU - Falco,C, AU - Gilabert,J, AU - España,F, AU - Cano,A, AU - Segui,R, AU - Aznar,J, PY - 1999/5/11/pubmed PY - 1999/5/11/medline PY - 1999/5/11/entrez SP - 516 EP - 21 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 81 IS - 4 N2 - 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. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/10235431/Plasminogen_activator_inhibitor_1__PAI_1__promoter_4G/5G_genotype_and_increased_PAI_1_circulating_levels_in_postmenopausal_women_with_coronary_artery_disease_ DB - PRIME DP - Unbound Medicine ER -