Genotype combinations of plasminogen activator inhibitor-1 and angiotensin-converting enzyme genes and risk for early onset of coronary heart disease.

摘要

BACKGROUND: Both angiotensin-converting enzyme genotype and plasminogen activator inhibitor type 1 genotype have an effect on fibrinolytic components and hence, may increase risk or advance occurrence of coronary heart disease. We examined the association of the angiotensin-converting enzyme and the plasminogen activator inhibitor type 1 genotypes, and their combinations, with early onset of coronary heart disease in a cohort of 907 patients with coronary heart disease. DESIGN AND METHODS: All patients with a coronary heart disease (International Classification of Diseases, 9th Rev. pos. 410-414), aged 30-70 years and participating in an inpatient rehabilitation program between January 1999 and May 2000 in two clinical centres in Germany were enrolled. The plasminogen activator inhibitor type 1 and the angiotensin-converting enzyme genotypes were determined by polymerase chain reaction, and the distribution was compared between patients with early (< or =55 years) and late (>55 years) onset of coronaryheart disease. A multivariate analysis was employed to adjust for potentially confounding factors. RESULTS: Of the 907 included patients, 408 (45.0%) developed coronary heart disease before the age of 55 years. For the 4G/4G genotype of plasminogen activator inhibitor type 1 the odds ratio for early onset of coronary heart disease was 1.68 [95% confidence interval (CI) 1.01-2.57] and for the D/D genotype of angiotensin-converting enzyme the odds ratio was 1.22 (95% CI 0.84-1.76) after adjustment for covariates. In multivariate analysis an odds ratio of 3.10 (95% CI 1.51-6.36) was found for the association between the combined homozygosity for both polymorphisms (plasminogen activator inhibitor type 1 genotype 4G/4G and angiotensin-converting enzyme genotype D/D) and onset of coronary heart disease before the age of 55 years after controlling for sex, age, smoking, diabetes, hypertension, hyperlipidemia and school education. CONCLUSION: The co-existence of the 4G/5G polymorphism of the plasminogen activator inhibitor type 1 gene and the I/D polymorphism of the angiotensin-converting enzyme gene increases the risk for early onset of coronary heart disease in this population.