PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants.
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.
Margaglione
M
M
Unita' di Trombosi e Aterosclerosi, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
Cappucci
G
G
d'Addedda
M
M
Colaizzo
D
D
Giuliani
N
N
Vecchione
G
G
Mascolo
G
G
Grandone
E
E
Di Minno
G
G
D000328:Adult; D000368:Aged; D000375:Aging; D000428:Alcohol Drinking; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D012907:Smoking; D014280:Triglycerides / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A