A population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1.
BACKGROUND
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.


METHODS
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.
Williams
Scott M
SM
Center for Human Genetics Research, 519 Light Hall, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA. smwilliams@chgr.mc.vanderbilt.edu
Stocki
Shelli
S
Jiang
Lan
L
Brew
Kwabena
K
Gordon
Seth
S
Vaughan
Douglas E
DE
Brown
Nancy J
NJ
Poku
Kwabena A
KA
Moore
Jason H
JH
D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005869:Ghana; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator