Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1

D. K. Kim, J. W. Kim, S. Kim, H. C. Gwon, J. C. Ryu, J. E. Huh, Jina Choo, Y. Choi, C. H. Rhee, W. R. Lee

Research output: Contribution to journalArticle

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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 analysts 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.

Original languageEnglish
Pages (from-to)3242-3247
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number11
Publication statusPublished - 1997 Dec 1
Externally publishedYes

Fingerprint

Plasminogen Activator Inhibitor 1
Peptidyl-Dipeptidase A
Genes
Genotype
Angiotensin II
Alleles
Fibrinolysis
Coronary Artery Disease
Analysis of Variance
Antigens
Messenger RNA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1. / Kim, D. K.; Kim, J. W.; Kim, S.; Gwon, H. C.; Ryu, J. C.; Huh, J. E.; Choo, Jina; Choi, Y.; Rhee, C. H.; Lee, W. R.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 17, No. 11, 01.12.1997, p. 3242-3247.

Research output: Contribution to journalArticle

Kim, DK, Kim, JW, Kim, S, Gwon, HC, Ryu, JC, Huh, JE, Choo, J, Choi, Y, Rhee, CH & Lee, WR 1997, 'Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 11, pp. 3242-3247.
Kim, D. K. ; Kim, J. W. ; Kim, S. ; Gwon, H. C. ; Ryu, J. C. ; Huh, J. E. ; Choo, Jina ; Choi, Y. ; Rhee, C. H. ; Lee, W. R. / Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 ; Vol. 17, No. 11. pp. 3242-3247.
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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 analysts 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.",
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AU - Huh, J. E.

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AU - Lee, W. R.

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