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

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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.

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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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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA

    J. A. Schoenhard, D. E. Vaughan & Scott M. Williams

  2. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    F. W. Asselbergs

  3. Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    F. W. Asselbergs

  4. Human Services Management and Public Administration, Business School, University of Ghana, Legon, Ghana

    K. A. Poku

  5. Departments of Genetics and Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA

    S. A. Stocki & J. H. Moore

  6. Regional Hospital, Sunyani, Ghana

    S. Gordon

  7. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA

    N. J. Brown

  8. Center for Human Genetics Research, 519 Light Hall, Vanderbilt University, Nashville, TN, 37232, USA

    Scott M. Williams

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  1. J. A. Schoenhard
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  2. F. W. Asselbergs
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  3. K. A. Poku
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  4. S. A. Stocki
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  5. S. Gordon
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  6. D. E. Vaughan
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  7. N. J. Brown
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  8. J. H. Moore
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  9. Scott M. Williams
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Correspondence to Scott M. Williams.

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J. A. Schoenhard and F. W. Asselbergs have contributed equally to this manuscript.

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Schoenhard, J.A., Asselbergs, F.W., Poku, K.A. et al. Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Hum Genet 124, 479–488 (2008). https://doi.org/10.1007/s00439-008-0573-x

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  • DOI: https://doi.org/10.1007/s00439-008-0573-x

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