Genetic variation-optimized treatment benefit of angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: a 12-year follow-up study.

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.

• Authors: Jen-Kuang Lee, Cho-Kai Wu, Chia-Ti Tsai, Lian-Yu Lin, Jou-Wei Lin, Kuo-Liong Chien, Juey-Jen Hwang, Chunn-Lee Lin, Chuen-Den Tseng, Fu-Tien Chiang
• Journal: Pharmacogenetics and genomics (Pharmacogenet Genomics) Vol. 23 Issue 4 Pg. 181-9 (Apr 2013) ISSN: 1744-6880 [Electronic] United States
• PMID: 23407050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AGTR1 protein, human
• Angiotensin-Converting Enzyme Inhibitors
• Receptor, Angiotensin, Type 1
• Peptidyl-Dipeptidase A

Topics

• Angiotensin-Converting Enzyme Inhibitors (administration & dosage)
• Coronary Artery Disease (drug therapy, genetics, pathology)
• Female
• Follow-Up Studies
• Genotype
• Haplotypes
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (genetics)
• Polymorphism, Genetic
• Proportional Hazards Models
• Receptor, Angiotensin, Type 1 (genetics)
• Renin-Angiotensin System (drug effects, genetics)