title: Contribution of the type 1 plasminogen activator inhibitor 4G/5G gene polymorphism to impaired fibrinolysis in vital exhaustion.
abstract: BACKGROUND
  Inappropriate coping with chronic stress may result in a state of "vital exhaustion" that has been associated with coronary artery disease. Impaired fibrinolysis due to an increase in type 1 plasminogen activator inhibitor (PAI-1) might mediate this link. Genetic and environmental factors both regulate the plasma PAI-1 levels. We investigated the contribution of the PAI-1 4G/5G gene polymorphism to the plasma levels of PAI-1 in exhaustion.
  
  
  METHODS
  The study participants were 258 (mean age 40.9 +/- 9.1 years) apparently healthy subjects of an airplane manufacturing plant in Germany who completed the Shortened 9-item Maastricht Vital Exhaustion Questionnaire. A median split was performed on exhaustion scores rendering two groups of exhausted and non-exhausted subjects. The PAI-1 4G/5G polymorphism in the promoter region of the PAI-1 gene and several variables related to the insulin resistance syndrome known to affect plasma PAI-1 levels were assessed.
  
  
  RESULTS
  Across all subjects, exhausted individuals had higher PAI-1 antigen levels than non-exhausted subjects (46.6 +/- 20.7 vs 38.3 +/- 21.4 ng/ml, p = 0.002). There were no significant differences in the PAI-1 antigen levels between exhausted and non-exhausted individuals with both the 4G/4G and the 4G/5G polymorphism. With the 5G/5G polymorphism, however, exhausted subjects had higher PAI-1 antigen levels than non-exhausted subjects (44.9 +/- 22.9 vs 31.2 +/- 13.1 ng/ml, p = 0.017). These results did not change when controlling for the variables of insulin resistance.
  
  
  CONCLUSIONS
  The findings suggest that the PAI-1 4G/5G gene polymorphism might affect the plasma PAI-1 levels related to exhaustion severity. With the 5G/5G polymorphism, exhausted subjects might have less fibrinolytic capacity than non-exhausted subjects.
authors.affiliation: Institute for Behavioral Sciences, Swiss Federal Institute of Technology, University Hospital, Zürich, Switzerland. roland.vonkaenel@ifv.gess.etzh.ch
authors.forename: Roland
authors.initials: R
authors.lastname: von Känel
authors.forename: Friedrich E
authors.initials: FE
authors.lastname: Maly
authors.forename: Karl
authors.initials: K
authors.lastname: Frey
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Fischer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D001824:Body Constitution / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D005221:Fatigue / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors