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


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 coronary heart 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.


CONCLUSIONS
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.
Loew
Michael
M
Department of Epidemiology, German Centre for Research on Ageing, University of Heidelberg, Heidelberg, Germany.
Hoffmann
Michael M
MM
Hahmann
Harry
H
Maerz
Winfried
W
Brenner
Hermann
H
Rothenbacher
Dietrich
D
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D003327:Coronary Disease / Q000235:genetics* / Q000534:rehabilitation; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
D017395:Plasminogen Activator Inhibitor 1; D007703:Peptidyl-Dipeptidase A