The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin system in determining plasma t-PA and PAI-I 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) 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-I 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 renin-angiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI- I (P < 0.01) compared to females. When stratifying females by menopausal status, PAI-I 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-I in both females and males, and that the regression relationships between these factors and plasma t-PA and PAI-I were dependent on gender. In addition, we found that the PAI-I 4G/5G polymorphism was a significant predictor of PAI-I levels in both females and males, that the angiotensin II type 1 receptor A1166C was a significant predictor of t-PA and PAI-I levels in females, and that the brodykinin 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-I 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-I is different between females and males.

Original languageEnglish (US)
Pages (from-to)471-477
Number of pages7
JournalThrombosis and Haemostasis
Volume96
Issue number4
DOIs
StatePublished - Oct 2006

Keywords

  • Epidemiological studies
  • Plasminogen
  • Risk factors
  • Sex
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

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