PAI-1 4G/5G and ACE I/D gene polymorphisms and the occurrence of myocardial infarction in patients on intermittent dialysis

Background. Myocardial infarction (MI) is a leading cause of death, particularly in high-risk settings such as uraemia, in which it is not yet known to what extent genetic factors contribute to the overall risk of MI. We have prospectively evaluated the effect of plasminogen activator inhibitor-1 (PAI-1) 4G/5G and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the occurrence of MI in uraemics. Methods. All patients undergoing intermittent dialysis in an Italian district were enrolled as subjects. From the same area, 1307 individuals served as controls. Genomic DNA was obtained and ACE I/D and PAI-1 4G/5G gene polymorphisms were determined. After a baseline evaluation, patients were followed for 28.8 +/- 9.8 months. MIs and other causes of death were recorded. Results. A total of 461 patients (417 on haemodialysis and 44 on peritoneal dialysis) were investigated. At entry, their mean age was 58.2 +/- 16.2 years and dialytic age was 82 +/- 69 months. Genotype frequencies were not different between controls and uraemics and, in the latter group, between patients with or without cardiovascular diseases at baseline evaluation. During the follow-up, 22 fatal and 16 non-fatal MIs were recorded (mean incidence 1.99 and 1.45%/year, respectively). The adjusted risk of fatal and total MI was related to the presence at entry of a history of MI [hazard ratios (HR) 4.3; 95% confidence interval (CI) 1.5-12.0 and HR 6.8; 95% Cl: 3.3-14.0, respectively] and to the PAI-1 4/4 genotype (HR 2.8; 95% CI 1.2-6.9 and HR 2.1; 95% CI 1.1-4.2, respectively). Conclusions. In end-stage renal disease, PAI-1 4G/5G gene polymorphism may have a significant role in the occurrence of fatal and non-fatal MI.