Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease.
OBJECTIVE
The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients.


METHODS
Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models.


RESULTS
Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D was associated with a higher rate of MACE in a multivariate regression analysis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p < 0.001]. This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE in hibitors*ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014).


CONCLUSIONS
The use of ACE inhibitors was associated with a significant decrease in MACE in hypertensive patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.


BACKGROUND
Angiotensin-converting enzyme inhibitors; Coronary artery disease; Hypertension; Pharmacogenetic.
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei;
Cho-Kai
CK
Wu
Department of Clinical Pathology & Cardiovascular Center;
Jen-Kuang
JK
Lee
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;
Lian-Yu
LY
Lin
Department of Family Medicine and Health Management Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Yin-Tsen
YT
Huang
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;
Juey-Jen
JJ
Hwang
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;
Chunn-Lee
CL
Lin
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;
Chuen-Den
CD
Tseng
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital;
Fu-Tien
FT
Chiang