Renin-angiotensin system genes polymorphisms and long-term prognosis in taiwanese patients with hypertension and coronary artery disease

Objectives: The objective of this study was to evaluate the renin-an giotensin system genetic ef fects and pharmacogenetic in teractions for angioten sin-con vertingenzyme (ACE) in hibitors in hypertensive coronaryartery 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 an gio ten sin II type I re cep tor gene (AGT1R)] were col lected. Pa tients were as signed to 2 groups (ACE in hib i tor or No-ACE in hib i tor) and fol lowed-for up to 12 years. Kaplan-Meier curves and Cox re gres sion mod els were used to dem on strate the sur vival and ma jor car dio vas cu lar events (MACE) event-free sur vival trends. Pharmacogenetic ef fects were determined by several Cox regression models. Re sults: Of the 518 pa tients in our study, 290 were treated with ACE in hib i tors and 228 were not. Pre scrip tion of ACE in hib i tors was as so ci ated with a lower rate of MACE at 4000 days. In ad di tion, ACE I/D gene D was as so ci ated with a higher rate of MACE in a multivariate re gres sion anal y sis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p < 0.001]. This ef fect could be at ten u ated by the pharmacogenetic in ter ac tion of ACE in hib i tors and the ACE gene (ACE in hibitors ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014). Con clu sions: The use of ACE in hib i tors was as so ci ated with a sig nif i cant de crease in MACE in hy per ten sive pa tients di ag nosed with CAD. Ge netic vari ants were also as so ci ated with event-free sur vival, but their ef fects were modified by the use of ACE inhibitors.