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; 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:10.1160/TH06-06-0335

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands

,

Scott M. Williams

²Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, USA

,

Patricia R. Hebert

³Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conneticut, USA

,

Christopher S. Coffey

⁴Department of Biostatistics, School of Public Health, University of Alabama Birmingham, Birmingham, Alabama, USA

,

Hans L. Hillege

¹Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands

,

Gerjan Navis

⁵Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands

,

Douglas E. Vaughan

²Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, USA

,

Wiek H. van Gilst

¹Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands

⁶Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, the Netherlands

,

Jason H. Moore

⁷Departments of Genetics and Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA

› Author Affiliations

Abstract

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

Full Text

References

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