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

Schoenhard JA, Asselbergs FW, Poku KA, Stocki SA, Gordon S, Vaughan DE, Brown NJ, Moore JH, Williams SM
Hum Genet. 2008 124 (5): 479-88

PMID: 18953568 · PMCID: PMC2770717 · DOI:10.1007/s00439-008-0573-x

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.

MeSH Terms (17)

Adult Blood Glucose Blood Pressure Cholesterol Female Fibrinolysis Ghana Humans Male Middle Aged Models, Genetic Plasminogen Activator Inhibitor 1 Polymorphism, Genetic Renin-Angiotensin System Sex Characteristics Tissue Plasminogen Activator Triglycerides

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