© 1997 American Heart Association, Inc.
Articles |
Polymorphism of Angiotensin Converting Enzyme Gene Is Associated With Circulating Levels of Plasminogen Activator Inhibitor-1
Correspondence to Won-Ro Lee, MD, PhD, Division of Cardiology, Department of Medicine, Samsung Medical Center, Sung Kyun Kwan University, College of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135–230, Korea. E-mail dkkim{at}smc.samsung.co.kr
Abstract The deletion (D) allele of the
insertion/deletion (I/D) polymorphism of the
angiotensin converting enzyme (ACE) gene is strongly
associated with an increased level of circulating ACE. The ACE gene
polymorphism may influence the production of
angiotensin II (Ang II). It has been shown that Ang II
modulates fibrinolysis, that is, Ang II increases
plasminogen activator inhibitor-1
(PAI-1) mRNA and plasma PAI-1 levels in vitro and in vivo. Considered
together, we tested the hypothesis that the deletion allele of the
ACE gene might be associated with increased levels of PAI-1. We related
the ACE genotype to PAI-1 antigen levels in 603
men and 221 women attending a routine health screening. As a whole, the
plasma PAI-1 level was not strongly associated with ACE
genotype. Since the PAI-1 level was significantly influenced by
well-known risk factors for coronary artery disease (CAD), we
further analyzed the data after excluding subjects with major
cardiovascular risk factors. In low-risk male subjects,
the DD genotype had significantly higher levels
of plasma PAI-1 (DD: 20.3±2.2; DI: 13.9±1.1; II: 13.6±1.3 ng/mL,
P=.010 by ANOVA). In low-risk female subjects, the
DD genotype showed a tendency to a high level of
plasma PAI-1 without statistical significance. When analysis
was restricted to postmenopausal women (age
55 or FSH35 ng/mL), the
DD genotype showed a significantly higher level
of PAI-1 than subjects with the DI and II
genotypes (27.7±6.2 versus 15.6±1.8 ng/mL,
P=.028). The DD polymorphism of the ACE gene is
associated with high PAI-1 levels in male and possibly in
postmenopausal female subjects who have lower conventional
cardiovascular risk factors. These results suggest that
the increased ACE activity caused by DD polymorphism may play an
important role in elevating the level of plasma PAI-1. Our data support
the notion that the genetic variation of ACE contributes to the balance
of the fibrinolytic pathway.
Key Words: angiotensin converting enzyme • polymorphism • plasminogen activator inhibitor-1 • renin-angiotensin system
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