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

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
JournalHuman Genetics
Volume124
Issue number5
DOIs
StatePublished - Oct 27 2008

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Schoenhard, J. A., Asselbergs, F. W., Poku, K. A., Stocki, S. A., Gordon, S., Vaughan, D. E., Brown, N. J., Moore, J. H., & Williams, S. M. (2008). Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Human Genetics, 124(5), 479-488. https://doi.org/10.1007/s00439-008-0573-x