Author:
Kim Duk-Kyung,Kim Jong-Won,Kim Seonwoo,Gwon Hyeon-Cheol,Ryu Jae-Choon,Huh Jeong-Eun,Choo Jin-A,Choi Youngran,Rhee Chong-Heon,Lee Won-Ro
Abstract
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 FSH≥35 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
70 articles.
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