Plasminogen activator inhibitor-1 (PAI-1) antigen plasma levels in subjects attending a metabolic ward: Relation to polymorphisms of PAI-1 and angiontensin converting enzyme (ACE) genes

Maurizio Margaglione, Elvira Grandone, Gennaro Vecchione, Giuseppe Cappucci, Nicola Giuliani, Donatella Colaizzo, Egidio Celentano, Salvatore Panico, Giovanni Di Minno

Research output: Contribution to journalArticle

Abstract

Plasminogen activator inhibitor 1 (PAI-1) is a determinant of vascular events. Subjects in metabolic wards are at high risk for these events. The renin-angiotensin system modulates plasma PAI-1 levels. An insertion (4G)/deletion (5G) polymorphism is involved in the regulation of the circulating levels of PAI-1. We have evaluated the levels of plasma PAI-1 in 208 individuals from our metabolic ward and correlated these levels with the 4G/5G genotype as well as with a genotype (homozygosity for a deletion polymorphism, DD genotype) of the angiotensin-converting enzyme (ACE) gene. Homozygosity for the insertion genotype (5G/5G) was associated with PAI-1 levels lower than those associated with the deletion genotype (4G/4G) (26.2x/:1.6 versus 33.7x/: 1.7 ng/mL, P=.036). Plasma PAI-1 levels appeared to depend on the genotype (P=.014) as much as on age (P=.044), t-PA (P=.0001), or triglyceride levels (P=.005). The association between triglycerides and PAI-1 was significant in subjects carrying the 4G/4G and the 4G/5G genotypes (P=.013 and .036, respectively) but not in those with the 5G/5G genotype. When stratified according to PAI-1 and ACE genotypes, individuals homozygous for both deletions (4G/4G-DD genotypes) exhibited higher plasma PAI-1 levels compared with those of individuals without such homozygosities. However, this difference did not reach statistical significance. We conclude that in a group of subjects from a metabolic ward, a 4G/SG polymorphism of the PAI-1 gene exerts effects on plasma PAI-1 antigen levels comparable to those of established determinants. The association between triglycerides and plasma PAI-1 levels is genotype dependent. A trend to a positive interaction between ACE DD and PAI-1 4G/4G in the regulation of circulating plasma PAI-1 levels is present in this setting.

Original languageEnglish
Pages (from-to)2082-2087
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number10
Publication statusPublished - 1997

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Keywords

  • Cross-sectional study
  • Genotype-environment interaction
  • Inhibitor 1
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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