title: An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke.
abstract: OBJECTIVE
  The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids.
  
  
  METHODS
  We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined.
  
  
  RESULTS
  The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95% CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95% CI, 2.4-105.0).
  
  
  CONCLUSIONS
  This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.
authors.affiliation: Cerebrovascular Diseases Unit, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
authors.forename: Antonella
authors.initials: A
authors.lastname: Bodini
authors.forename: Carla
authors.initials: C
authors.lastname: Brambilla
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Carriero
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Parati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000097:blood / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D002784:Cholesterol