title: Contribution of genetic and metabolic syndrome to omental adipose tissue PAI-1 gene mRNA and plasma levels in obesity.
abstract: BACKGROUND
  Plasminogen activator inhibitor type-1 (PAI-1) has already been associated with atherosclerosis; myocardial infarction; and cardiovascular disease risk factors such as obesity, insulin resistance, and dyslipidemia. However, factors regulating PAI-1 adipose tissue (AT) gene expression and plasma levels are not yet well defined.
  
  
  OBJECTIVE
  This study aims to assess the contribution of PAI-1 omental AT mRNA levels and genetic and metabolic factors to variation in plasma PAI-1 concentrations.
  
  
  METHODS
  Ninety-one non-diabetic premenopausal severely obese women (body mass index, BMI >35 kg/m(2)) undergoing bariatric surgery were phenotyped (fasting plasma glucose, lipid-lipoprotein, and PAI-1 levels) and genotyped for four PAI-1 polymorphisms. Omental AT PAI-1 mRNA levels were determined using real-time polymerase chain reaction. Stepwise regression analysis was used to identify independent PAI-1 AT mRNA and plasma level predictors.
  
  
  RESULTS
  Among the variables included to the stepwise regression analysis, plasma high-density lipoprotein (HDL)-cholesterol (r = 0.38; p = 0.0004) and total cholesterol (r = 0.16; p = 0.0541) levels were the only two (out of 12) independent variables retained as predictive of PAI-1 omental AT mRNA levels, whereas BMI (r = 0.35; p = 0.0039), plasma HDL-cholesterol concentrations (r = -0.31; p = 0.0375), PAI-1 omental AT mRNA levels (r = 0.19; p = 0.0532) and PAI-1-844G/A (p = 0.0023), and rs6092 (p.A15T; p = 0.0358) polymorphisms contributed independently to plasma PAI-1 concentrations. Taken together, these variables explained 17.8% and 31.0% of the variability in PAI-1 AT mRNA and plasma levels, respectively.
  
  
  CONCLUSIONS
  These results suggest that PAI-1 polymorphisms contribute significantly to PAI-1 plasma levels but do not support the notion that omental AT is one of its major source.
authors.affiliation: Department of Medicine, ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Université de Montréal, Saguenay, QC, Canada. luigi.bouchard@recherche-caurc.org
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: Stéfane
authors.initials: S
authors.lastname: Lebel
authors.forename: Frédéric-Simon
authors.initials: FS
authors.lastname: Hould
authors.forename: Picard
authors.initials: P
authors.lastname: Marceau
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Pascale
authors.initials: P
authors.lastname: Mauriège
mesh_terms: D050153:Abdominal Fat / Q000737:chemistry*; D000328:Adult; D005260:Female; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D009852:Omentum / Q000737:chemistry*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human