Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke.
BACKGROUND
The 4G allele in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene is associated with higher plasma PAI-1 levels and activity, but its association with cardiovascular diseases is unclear. We investigated the association of polymorphisms and common haplotypes of the PAI-1 gene with plasma PAI-1 levels, as well as the risk of myocardial infarction and stroke.


RESULTS
This study is a prospective analysis of 2995 community-based participants (41% blacks and 51% women) aged 70 to 79 years old in the Health, Aging, and Body Composition Study. From 1997/1998 to 2001, 177 myocardial infarction events and 101 stroke events were identified. In addition to the 4G/5G polymorphism, 2 potential functional variants and other 4 haplotype-tagging variants were genotyped. In general linear models, the 4G allele was associated with higher PAI-1 levels after adjusting for age, sex, race, and site (26, 29, and 32 ng/mL for 5G/5G, 4G/5G, and 4G/4G, respectively; P for trend < .0001), but none of the other 6 polymorphisms was associated with PAI-1 levels. Haplotype analysis produced similar results. However, in Cox proportional hazard models, neither the polymorphisms nor the common haplotypes of the PAI-1 gene was associated with the risk of either myocardial infarction or stroke.


CONCLUSIONS
The 4G allele is associated with higher PAI-1 levels, but this study does not support an association of the PAI gene polymorphisms with the risk of either myocardial infarction or stroke.
Ding
Jingzhong
J
Department of Internal Medicine/Geriatrics, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA. jding@wfubmc.edu
Nicklas
Barbara J
BJ
Fallin
Margaret D
MD
de Rekeneire
Nathalie
N
Kritchevsky
Stephen B
SB
Pahor
Marco
M
Rodondi
Nicolas
N
Li
Rongling
R
Zmuda
Joseph M
JM
Harris
Tamara B
TB
D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D020521:Stroke / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1