PAI-1 PLASMA-LEVELS IN A GENERAL-POPULATION WITHOUT CLINICAL-EVIDENCEOF ATHEROSCLEROSIS - RELATION TO ENVIRONMENTAL AND GENETIC-DETERMINANTS

Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been cons istently related to a polymorphism (4G/5G) of the PAI-1 gene. The reni n-angiotensin pathway plays a role in the regulation of PAI-1 plasma l evels. An insertion (I)/deletion (D) polymorphism of the angiotensin-c onverting enzyme (ACE) gene has been related to plasma and cellular AC E levels. In 1032 employees (446 men and 586 women; 22 to 66 years old ) of a hospital in southern Italy, we investigated the association bet ween PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antige n levels. None of the individuals enrolled had clinical evidence of at herosclerosis, 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). M ultivariate analysis documented the independent effect on PAI-1 plasma levels of body mass index (P<.001), triglycerides (P<.001), sex (P<.0 01), PAI-1 4G/5G polymorphism (P=.019), smoking habit (P=.041), and AC E I/D genotype (P=.042). Thus, in addition to the markers of insulin r esistance and smoking habit, gene variants of PAI-1 and ACE account fo r a significant portion of the between-individual variability of circu lating PAI-1 antigen concentrations in a general population without cl inical evidence of atherosclerosis.