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Thromb Haemost 2006; 96(04): 471-477
DOI: 10.1160/TH06-06-0335
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels

Folkert W. Asselbergs
1   Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
,
Scott M. Williams
2   Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, USA
,
Patricia R. Hebert
3   Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conneticut, USA
,
Christopher S. Coffey
4   Department of Biostatistics, School of Public Health, University of Alabama Birmingham, Birmingham, Alabama, USA
,
Hans L. Hillege
1   Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
,
Gerjan Navis
5   Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands
,
Douglas E. Vaughan
2   Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, USA
,
Wiek H. van Gilst
1   Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
6   Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, the Netherlands
,
Jason H. Moore
7   Departments of Genetics and Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA
› Author Affiliations
Further Information

Publication History

Received 16 June 2006

Accepted after revision 25 August 2006

Publication Date:
29 November 2017 (online)

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Summary

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-1 levels in a large population-based sample from the PREVEND study in Groningen, the Netherlands (n=2,527). We measured polymorphisms from genes of the fibrinolytic system, the reninangiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI-1 (P < 0.01) compared to females. When stratifying females by menopausal status, PAI-1 levels were only significantly different between pre-menopausal females and males (p<0.001). Furthermore, we found that age, body mass index, and waist-to-hip ratio were significant predictors of t-PA and PAI-1 in both females and males, and that the regression relationships between these factors and plasma t-PA and PAI-1 were dependent on gender. In addition, we found that the PAI-1 4G/5G polymorphism was a significant predictor of PAI-1 levels in both females and males, that the angiotensin II type I receptor A1166C wasa significant predictor of t-PA and PAI-1 levels in females, and that the bradykinin receptor B2 58CT polymorphism was a significant predictor of t-PA levels in females. In conclusion, this large population-based study showed that t-PA and PAI-1 levels are determined by several demographic and genetic factors involved in the fibrinolytic, RAS and bradykinin system. In addition, the results support the idea that the biology of t-PA and PAI-1 is different between females and males.

Keywords

Epidemiological studies - thrombosis - risk factors - plasminogen - sex
 

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