title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine/Geriatrics, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA. jding@wfubmc.edu
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Nicklas
authors.forename: Margaret D
authors.initials: MD
authors.lastname: Fallin
authors.forename: Nathalie
authors.initials: N
authors.lastname: de Rekeneire
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Marco
authors.initials: M
authors.lastname: Pahor
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
mesh_terms: 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*
chemical_list: D017395:Plasminogen Activator Inhibitor 1