Contribution of the type 1 plasminogen activator inhibitor 4G/5G gene polymorphism to impaired fibrinolysis in vital exhaustion

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.