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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2082-2087.)
© 1997 American Heart Association, Inc.

Articles

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

From the Unita' di Trombosi e Aterosclerosi, IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Servizio di Epidemiologia, Istituto Tumori, Clinica Medica, Dipartimento di Medicina Clinica e Sperimentale, and Cattedra di Gerontologia e Geriatria, Università di Palermo, Italy.

Correspondence to Giovanni Di Minno, MD, Clinica Medica, Dipartimento di Medicina, Clinica e Sperimentale, Via S. Pansini, 5, 80131, Napoli, Italy.

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/5G 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.

Key Words: cross-sectional study • tissue plasminogen activator • tissue plasminogen activator • inhibitor 1 • genotype-environment interaction

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