Genetic variation-optimized treatment benefit of angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: A 12-year follow-up study
Journal
Pharmacogenetics and Genomics
Journal Volume
23
Journal Issue
4
Pages
181-189
Date Issued
2013
Author(s)
Lin C.-L.
Tseng C.-D.
Abstract
OBJECTIVES: The objective of this study was to examine the relationship between renin-angiotensin system genotypes and the pharmacogenetics of angiotensin-converting enzyme (ACE) inhibitors in Chinese patients with coronary artery disease (CAD). METHODS: Patients with angiographic CAD were recruited from 1995 to 2003. The baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphisms, six polymorphisms of the angiotensinogen (AGT) gene, and A-1166C polymorphisms of the angiotensin-II type I receptor gene (AGT1R)] were established. Patients were divided into two groups (ACE inhibitor or no ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to determine the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models. RESULTS: Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. ACE inhibitors were associated with a lower MACE rate at 4000 days. In addition, the ACE I/D gene D and AGT1R gene C alleles were associated with a higher MACE rate on the basis of a multivariate regression analysis. This effect was attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors* ACE gene, hazard ratio: 0.8, 95% confidence interval: 0.62-0.94, P=0.03). CONCLUSIONS: ACE inhibitors were associated with a significant decrease in MACE in Chinese patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors. ? 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.
SDGs
Other Subjects
angiotensin 1 receptor; angiotensinogen; dipeptidyl carboxypeptidase; dipeptidyl carboxypeptidase inhibitor; adult; allele; angiocardiography; article; cardiovascular disease; Chinese; confidence interval; controlled study; coronary artery disease; drug effect; event free survival; female; follow up; gene deletion; gene insertion; gene interaction; genetic polymorphism; genetic variability; genotype; hazard ratio; human; human tissue; Kaplan Meier method; major clinical study; male; multivariate logistic regression analysis; outcome assessment; pharmacogenetics; priority journal; proportional hazards model; renin angiotensin aldosterone system; statistical significance; survival
Publisher
Lippincott Williams and Wilkins
Type
journal article