Dk. Kim et al., POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENE IS ASSOCIATED WITHCIRCULATING LEVELS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1, Arteriosclerosis, thrombosis, and vascular biology, 17(11), 1997, pp. 3242-3247
The deletion (D) allele of the insertion/deletion (I/D) polymorphism o
f 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 s
hown that Ang II modulates fibrinolysis, that is, Ang II increases pla
sminogen 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 increase
d 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 w
hole, the plasma PAI-1 level was not strongly associated with ACE geno
type. Since the PAI-1 level was significantly influenced by well-known
risk factors for coronary artery disease (CAD), we further analyzed t
he data after excluding subjects with major cardiovascular risk factor
s. 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 st
atistical significance. When analysis was restricted to postmenopausal
women (age greater than or equal to 55 or FSH greater than or equal t
o 35 ng/mL), the DD genotype showed a significantly higher level of PA
I-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 as
sociated with high PAI-1 levels in male and possibly in postmenopausal
female subjects who have lower conventional cardiovascular risk facto
rs. These results suggest that the increased ACE activity caused by DD
polymorphism may play an important role in elevating the level of pla
sma PAI-1. Our data support the notion that the genetic variation of A
CE contributes to the balance of the fibrinolytic pathway.