Angiotensin converting enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasminogen activator inhibitor-1 in healthy Japanese population.
Plasminogen activator inhibitor-1 (PAI-1) has a central role in the regulation of the fibrinolytic enzyme system. An elevated plasma PAI-1 level is associated with thrombotic disorders. In vitro and in vivo studies indicate that the renin-angiotensin system is involved in the regulation of PAI-1. A 287-bp insertion/deletion (I/D) polymorphism in the gene-encoding angiotensin converting enzyme (ACE) is associated with cardiovascular disorders. We evaluated the association between the ACE I/D polymorphism and plasma PAI-1 antigen levels in 110 healthy Japanese male subjects. Subjects with the D-allele of the gene-encoding ACE had higher levels of PAI-1 (26.3 +/- 14.7 ng/ml, mean +/- standard deviation) compared with those without (21.0 +/- 12.0; P = 0.0491). A multiple linear regression model with independent variables (age, body-mass index, total cholesterol level, triglyceride level, ACE I/D genotype, and PAI-1 genotype due to a single guanine I/D polymorphism in the PAI-1 gene) demonstrated that the triglyceride level (P = 0.0059) and ACE I/D genotype (P = 0.0372) were independent predictors of plasma PAI-1 antigen levels in a subset of the subjects without diabetes mellitus that were not taking lipid-lowering drugs. These findings suggest that the ACE I/D polymorphism is a genetic factor for the regulation of plasma PAI-1 antigen levels in the healthy Japanese population.
Matsubara
Y
Y
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hayakawa
T
T
Tsuda
T
T
Takeshita
E
E
Watanabe
G
G
Murata
M
M
Watanabe
K
K
Ikeda
Y
Y
D000328:Adult; D000941:Antigens / Q000097:blood*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014280:Triglycerides / Q000097:blood; D014652:Vascular Diseases / Q000209:etiology
D000941:Antigens; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A