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Human Genetics

, Volume 124, Issue 5, pp 479–488 | Cite as

Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population

  • J. A. Schoenhard
  • F. W. Asselbergs
  • K. A. Poku
  • S. A. Stocki
  • S. Gordon
  • D. E. Vaughan
  • N. J. Brown
  • J. H. Moore
  • Scott M. Williams
Original Investigation

Abstract

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Caucasian subjects. The aim of this study was to identify the contributions of genetic and other factors to inter-individual variation in plasma levels of t-PA and PAI-1 in a large-scale population-based sample from urban West Africa. t-PA, PAI-1 and several demographic, anthropometric, and metabolic parameters were measured in 992 residents of Sunyani, the capital of the Brong-Ahafo region of Ghana. In addition, nine gene polymorphisms associated with components of the renin-angiotensin and fibrinolytic systems were determined. We found that BMI, systolic and diastolic blood pressure, total cholesterol, glucose, and triglycerides were all significant predictors of t-PA and PAI-1 in both females and males. In addition, a significant relationship was found between the PAI-1 4G/5G (rs1799768) polymorphism on PAI-1 levels in females, the TPA I/D (rs4646972) polymorphism on t-PA and PAI-1 in males, the renin (rs3730103) polymorphism on t-PA and PAI-1 in males, the ethanolamine kinase 2 (rs1917542) polymorphism on PAI-1 in males, and the renin (rs1464816) polymorphism on t-PA in females and on PAI-1 in males. This study of urban West Africans shows that t-PA and PAI-1 levels are determined by both genetic loci of the fibrinolytic and renin-angiotensin systems and other factors often associated with cardiovascular disease, and that genetic factors differ between males and females.

Keywords

Renin Cardiac Risk Factor Traditional Cardiovascular Risk Factor Dominant Genetic Model Renin Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by NIH grants HL65234 (to SMW and JHM), HL065193 (to NJB), and HL60906 (to DEV). JAS was supported by ARN. FWA is a research fellow of the Netherlands Heart Foundation (2003T010) and the Dutch Inter University Cardiology Institute Netherlands (ICIN).

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • J. A. Schoenhard
    • 1
  • F. W. Asselbergs
    • 2
    • 3
  • K. A. Poku
    • 4
  • S. A. Stocki
    • 5
  • S. Gordon
    • 6
  • D. E. Vaughan
    • 1
  • N. J. Brown
    • 7
  • J. H. Moore
    • 5
  • Scott M. Williams
    • 1
    • 8
  1. 1.Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical SchoolNashvilleUSA
  2. 2.Department of CardiologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
  3. 3.Unit of Genetic Epidemiology and Bioinformatics, Department of EpidemiologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
  4. 4.Human Services Management and Public Administration, Business SchoolUniversity of GhanaLegonGhana
  5. 5.Departments of Genetics and Community and Family MedicineDartmouth Medical SchoolLebanonUSA
  6. 6.Regional HospitalSunyaniGhana
  7. 7.Division of Clinical Pharmacology, Department of MedicineVanderbilt University Medical SchoolNashvilleUSA
  8. 8.Center for Human Genetics Research, 519 Light HallVanderbilt UniversityNashvilleUSA

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