Browsing by Author "Vaughan, D.E."
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Item Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population(Human Genetics, 2008-11) 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.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. © Springer-Verlag 2008.Item A population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1(Ethnicity and Disease, 2007-02) Williams, S.M.; Stocki, S.; Jiang, L.; Brew, K.; Gordon, S.; Vaughan, D.E.; Brown, N.J.; Poku, K.A.; Moore, J.H.Introduction: Susceptibility to arterial thrombosis has a significant genetic component that is partly due to the expression of two proteins, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1), that directly influence thrombus formation and degradation. We have initiated a large-scale population-based study to characterize the genetic architecture of plasma t-PA and PAI-1 in Blacks from Sunyani, Ghana. Design: The design of the study is based on the recruitment of 2000 unrelated subjects who are ascertained without regard to chronic disease status. The analyses of the results will be done by dividing the data into two parts, a modeling set and a validation data set. This study design will facilitate the identification of genetic, environmental, and demographic factors that contribute to inter-individual variation in plasma levels of t-PA and PAI-1 in the population at-large. Results: We report the specifics of the study design, as well as phenotype information on the first 1000 subjects. Our results show that females and males differ significantly in several key measures, including PAI-1, BMI, total cholesterol, and systolic blood pressure. Conclusions: The data collected from this population-based study demonstrate significant sex differences in PAI-1 and critical factors that may influence risk of thrombosis. These samples will serve to inform the genetic analyses of t-PA and PAI- levels.