von Känel Roland, Maly Friedrich E, Frey Karl, Fischer Joachim E
Institute for Behavioral Sciences, Swiss Federal Institute of Technology, University Hospital, Zürich, Switzerland.
Ital Heart J. 2003 Nov;4(11):791-6.
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.
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.
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.
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.
对慢性应激应对不当可能导致“精力耗竭”状态，这与冠状动脉疾病有关。1型纤溶酶原激活物抑制剂（PAI-1）增加导致的纤维蛋白溶解功能受损可能介导了这种联系。遗传和环境因素均调节血浆PAI-1水平。我们研究了PAI-1 4G/5G基因多态性对精力耗竭时血浆PAI-1水平的影响。
研究对象为德国一家飞机制造工厂的258名（平均年龄40.9±9.1岁）表面健康的受试者，他们完成了简版9项马斯特里赫特精力耗竭问卷。根据精力耗竭得分进行中位数分割，分为精力耗竭组和非精力耗竭组。评估了PAI-1基因启动子区域的PAI-1 4G/5G多态性以及几个已知会影响血浆PAI-1水平的与胰岛素抵抗综合征相关的变量。
在所有受试者中，精力耗竭者的PAI-1抗原水平高于非精力耗竭者（46.6±20.7 vs 38.3±21.4 ng/ml，p = 0.002）。在具有4G/4G和4G/5G多态性的精力耗竭者和非精力耗竭者之间，PAI-1抗原水平无显著差异。然而，对于5G/5G多态性，精力耗竭者的PAI-1抗原水平高于非精力耗竭者（44.9±22.9 vs 31.2±13.1 ng/ml，p = 0.017）。在控制胰岛素抵抗变量后，这些结果没有改变。
研究结果表明，PAI-1 4G/5G基因多态性可能影响与精力耗竭严重程度相关的血浆PAI-1水平。对于5G/5G多态性，精力耗竭者的纤维蛋白溶解能力可能低于非精力耗竭者。
