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

Autor: Jason H. Moore, Nancy J. Brown, Scott M. Williams, John A. Schoenhard, Folkert W. Asselbergs, Douglas E. Vaughan, Scott D. Gordon, S. A. Stocki, Kwabena A. Poku
Rok vydání: 2008
Předmět:
Adult
Blood Glucose
Male
medicine.medical_specialty
medicine.medical_treatment
FRAMINGHAM OFFSPRING POPULATION
Population
Blood Pressure
BLOOD-PRESSURE
Biology
PLASMINOGEN-ACTIVATOR INHIBITOR-1
Ghana
Article
Renin-Angiotensin System
chemistry.chemical_compound
Insulin resistance
Polymorphism (computer science)
Internal medicine
Plasminogen Activator Inhibitor 1
Fibrinolysis
Genetics
medicine
Humans
education
Triglycerides
Genetics (clinical)
Sex Characteristics
INSULIN-RESISTANCE
education.field_of_study
Polymorphism
Genetic
Models
Genetic
PROTHROMBOTIC STATE
MENOPAUSAL AGE
IMPAIRED FIBRINOLYSIS
Middle Aged
medicine.disease
Cholesterol
Endocrinology
Blood pressure
MYOCARDIAL-INFARCTION
chemistry
Tissue Plasminogen Activator
Plasminogen activator inhibitor-1
RISK-FACTORS
Female
RENIN-ANGIOTENSIN
Plasminogen activator
Sex characteristics
Zdroj: HUMAN GENETICS, 124(5), 479-488. SPRINGER
ISSN: 1432-1203
0340-6717
DOI: 10.1007/s00439-008-0573-x
Popis: 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.
Databáze: OpenAIRE
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