Abstract 3691: Genetic Polymorphisms in the ACE Gene and the GJA4 Gene Modify ACE-inhibitor Efficacy in Post-ACS Patients
Background ACE inhibitor therapy slows atherosclerosis and improves outcomes among patients with coronary disease. A polymorphism in the connexin-37 gene (GJA4) has been associated with the risk of coronary disease, myocardial infarction, and prognosis after an acute coronary syndrome (ACS). This raises the question of whether ACE-inhibitor efficacy may be modulated by GJA4 genotype. ACE inhibitor efficacy has also been inconsistently linked to the ACE insertion/deletion (ACE I/D) polymorphism. We sought to assess the impact of genotype at GJA4 1019 C>T and ACE I/D on ACE inhibitor effect in ACS patients.
Hypothesis Polymorphisms at GJA4 1019 C>T and ACE I/D will impact ACE-inhibitor efficacy in terms of all cause mortality in ACS patients.
Methods Prospective cohort study of 735 ACS patients admitted to 2 Kansas City, Missouri medical centers between 3/2000 and 10/2001. Cox proportional hazards models of 3-year all-cause mortality adjusted for age, race, gender, ACS type, revascularization, history of heart failure, and ejection fraction were used to compare genotype groups, stratified by discharge ACE inhibitor status (n=210 No ACE-inhibitor, n=525 with ACE-inhibitor).
Results In adjusted models GJA4 1019 C>T genotype was significantly related to mortality among patients not prescribed ACE inhibitors (HR=6.4 for T carriers vs. CC, p= 0.017). There was no significant association among those discharged on an ACE inhibitor (HR=1.6 for T carriers vs. CC, p=0.11). An interaction term for GJA4 genotype by ACE inhibitor status was borderline significant (p=0.08). ACE I/D genotype was associated with mortality among those prescribed ACE inhibitors (HR=1.9 for Insertion carriers vs. DD, p=0.025), but not in patients not prescribed ACE inhibitors (HR=1.3 for Insertion carriers vs. DD, p=0.6). ACE I/D by ACE inhibitor interaction was not significant (p=0.74).
Conclusions The GJA4 1019 T allele is associated with a >6-fold risk of death in ACS patients not prescribed an ACE inhibitor, whereas no association was detected in patients prescribed ACE inhibitors. ACE I/D genotype did not interact with ACE inhibitor therapy. GJA4 1019 C>T genotype may be useful to predict which ACS patients will receive the greatest benefit from ACE-inhibitor therapy.