Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.
Hum Genet
; 124(5): 479-88, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-18953568
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tissue Plasminogen Activator
/
Plasminogen Activator Inhibitor 1
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Africa
Language:
En
Journal:
Hum Genet
Year:
2008
Document type:
Article
Affiliation country:
United States