PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) ANTIGEN PLASMA-LEVELS IN SUBJECTS ATTENDING A METABOLIC WARD - RELATION TO POLYMORPHISMS OF PAI-1AND ANGIOTENSIN-CONVERTING ENZYME (ACE) GENES

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 inser tion (4G)/deletion (5G) polymorphism is involved in the regulation of the circulating levels of PAI-1. We have evaluated the levels of plasm a PAI-1 in 208 individuals from our metabolic ward and correlated thes e levels with the 4G/5G genotype as well as with a genotype (homozygos ity for a deletion polymorphism, DD genotype) of the angiotensin-conve rting enzyme (ACE) gene. Homozygosity for the insertion genotype (5G/5 G) was associated with PAI-I levels lower than those associated with t he deletion genotype (4G/4G) (26.2x/:1.6 versus 33.7x/:1.7 ng/mL, P=.0 36). Plasma PAI-1 levels appeared to depend on the genotype (P=.014) a s 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 .03 6, respectively) but not in those with the 5G/5G genotype. When strati fied according to PAI-1 and ACE genotypes, individuals homozygous for both deletions (4G/4G-DD genotypes) exhibited higher plasma PAI-1 leve ls compared with those of individuals without such homozygosities. How ever, this difference did not reach statistical significance. We concl ude that in a group of subjects from a metabolic ward, a 4G/5G polymor phism of the PAI-1 gene exerts effects on plasma PAI-1 antigen levels comparable to those of established determinants. The association betwe en triglycerides and plasma PAI-1 levels is genotype dependent. A tren d to a positive interaction between ACE DD and PAI-1 4G/4G in the regu lation of circulating plasma PAI-1 levels is present in this setting.