Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

Folkert W Asselbergs; Scott M Williams; Patricia R Hebert; Christopher S Coffey; Hans L Hillege; Gerjan Navis; Douglas E Vaughan; Wiek H van Gilst; Jason H Moore

doi:10.1016/j.ygeno.2006.11.004

Back

Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

Journal article

Open access

Peer reviewed

Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

Folkert W Asselbergs, Scott M Williams, Patricia R Hebert, Christopher S Coffey, Hans L Hillege, Gerjan Navis, Douglas E Vaughan, Wiek H van Gilst and Jason H Moore

Genomics (San Diego, Calif.), Vol.89(3), pp.362-369

2007

DOI: 10.1016/j.ygeno.2006.11.004

PMCID: PMC1808222

PMID: 17207964

Files and links (1)

url

https://doi.org/10.1016/j.ygeno.2006.11.004View

Published (Version of record) Open Access

Abstract

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II type 1 receptor (AT1R). In addition, bradykinin can induce the release of t-PA through a B2 receptor mechanism. In the present study, we aimed to investigate the epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based sample ( n = 2527). We demonstrated a strong significant interaction within genetic variations of the bradykinin B2 gene ( P = 0.002) and between ACE and bradykinin B2 ( p = 0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels ( P = 0.006). In both females and males, the bradykinin B2 gene interacted with AT1R gene on plasma PAI-1 levels ( P = 0.026 and P = 0.039, respectively). In addition, the current study found a borderline significant interaction between PAI 4G5G and ACE I/D on plasma t-PA and PAI-1 levels. These results support the idea that the interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems might play an important role in t-PA and PAI-1 biology.

Epidemiology

Epistasis

Fibrinolysis

Gene-gene interaction

Plasminogen

Thrombosis

Details

Title: Subtitle: Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels
Creators: Folkert W Asselbergs - Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
Scott M Williams - Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA
Patricia R Hebert - Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
Christopher S Coffey - Department of Biostatistics, School of Public Health, University of Alabama, Birmingham, Birmingham, AL, USA
Hans L Hillege - Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
Gerjan Navis - Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
Douglas E Vaughan - Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA
Wiek H van Gilst - Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
Jason H Moore - Department of Genetics and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA
Resource Type: Journal article
Publication Details: Genomics (San Diego, Calif.), Vol.89(3), pp.362-369
DOI: 10.1016/j.ygeno.2006.11.004
PMID: 17207964
PMCID: PMC1808222
NLM abbreviation: Genomics
ISSN: 0888-7543
eISSN: 1089-8646
Publisher: Elsevier Inc
Language: English
Date published: 2007
Academic Unit: Biostatistics
Record Identifier: 9984214699602771

Metrics

29 Record Views

25 Times Cited - Web of Science