© 1998 American Heart Association, Inc.
Original Contributions |
PAI-1 Plasma Levels in a General Population Without Clinical Evidence of Atherosclerosis
Relation to Environmental and Genetic Determinants
From Unita' di Trombosi e Aterosclerosi, IRCCS Casa Sollievo della Sofferenza (M.M., G.C., M.d'A., D.C., N.G., G.V., G.M., E.G.), S Giovanni Rotondo; and Istituto di Gerontologia e Geriatria, Università di Palermo (G. Di M.), Italy.
Correspondence to Maurizio Margaglione, MD, Unità di Aterosclerosi e Trombosi, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo (FG) 71013, Italy.
Abstract—Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin pathway plays a role in the regulation of PAI-1 plasma levels. An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been related to plasma and cellular ACE levels. In 1032 employees (446 men and 586 women; 22 to 66 years old) of a hospital in southern Italy, we investigated the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antigen levels. None of the individuals enrolled had clinical evidence of atherosclerosis. In univariate analysis, PAI-1 levels were significantly higher in men (P<.001), alcohol drinkers (P<.001), smokers (P=.009), and homozygotes for the PAI-1 gene deletion allele (4G/4G) (P=.012). Multivariate analysis documented the independent effect on PAI-1 plasma levels of body mass index (P<.001), triglycerides (P<.001), sex (P<.001), PAI-1 4G/5G polymorphism (P=.019), smoking habit (P=.041), and ACE I/D genotype (P=.042). Thus, in addition to the markers of insulin resistance and smoking habit, gene variants of PAI-1 and ACE account for a significant portion of the between-individual variability of circulating PAI-1 antigen concentrations in a general population without clinical evidence of atherosclerosis.
Key Words: fibrinolytic activity • plasminogen activator inhibitor 1 • angiotensin-converting enzyme • gene variant
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