Lack of association between the angiotensin-converting enzyme insertion/deletion polymorphism and plasminogen activator inhibitor-1 antigen levels in the National Heart, Lung, and Blood Institute Family Heart Study.
Experimental and clinical research supports a direct link between activation of the renin-angiotensin system and production of plasminogen activator inhibitor-1 (PAI-1), the primary physiologic inhibitor of tissue plasminogen activator. Several studies have reported higher PAI-1 levels in individuals carrying the deletion (D) allele of the angiotensin-converting enzyme (ACE) gene. We investigated the association between ACE genotypes and plasma PAI-1 levels in a family study of 577 women and 428 men from four US communities. Participants were between 25 and 84 years of age without evidence of coronary heart disease (CHD). Mean geometric plasma PAI-1 levels adjusted for ethnicity were 17.4, 17.9, and 18.1 ng/ml in participants with the DD, insertion-deletion (ID), and II genotypes, respectively (P = 0.89 for difference). We found no associations between ACE I/D genotypes and plasma PAI-1 antigen concentrations in a subset of participants without major CHD risk factors (hypertension, hypercholesterolemia, overweight, smoking, diabetes) or in a small sample of African-Americans. Our findings suggest that the ACE insertion/deletion polymorphism has relatively little, if any, influence on circulating PAI-1 levels in the population at large.
Pankow
J S
JS
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, 27514, USA. jim_pankow@unc.edu
Arnett
D K
DK
Borecki
I B
IB
Hunt
S C
SC
Eckfeldt
J H
JH
Folsom
A R
AR
Djoussé
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000097:blood; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009316:National Institutes of Health (U.S.); D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology / Q000378:metabolism*; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D014481:United States
D000941:Antigens; D017395:Plasminogen Activator Inhibitor 1; D007703:Peptidyl-Dipeptidase A