Abstract 3690: UCP2 Genotype Influences Response to Post-Acute Coronary Syndrome Therapy
Background: Uncoupling proteins (UCPs) are involved in regulating insulin secretion, reactive oxygen species generation, and fatty acid transport. Neurohormonal inhibition with β-blockers (BB) and ACE inhibitors (ACEI) may modulate these activities with differing consequences depending on the patient population. We hypothesized that polymorphisms in the UCP2 gene would influence response to BB or ACEI after an acute coronary syndrome (ACS).
Methods: INFORM is a prospective cohort study of ACS patients with 1-year rehospitalization follow-up. A total of 642 DNA samples were available and UCP2 -866 G>A and Ala55Val were genotyped by pyrosequencing. We evaluated the effect of BB and ACEI using Cox proportional hazards models stratified by genotype including pre-specified covariates. Given our a priori expectations of differential effects in the milieu of diabetes, the models were also conducted stratified by history of diabetes. Interaction terms between genotype and BB or ACEI were assessed in unstratified models.
Results: Minor allele frequencies were 0.39 and 0.44 for -866A and 55Val, respectively. A significant interaction between the Val55Ala genotype and ACEI was identified for rehospitalization (p=0.02), which was not influenced by the presence of diabetes. Among Val55Val subjects there was an increased risk of rehospitalization with ACEI (HR 3.5, p=0.02) compared to those who did not receive discharge ACEI. Among diabetic individuals, a significant interaction between -866 G >A genotype and BB was found for cardiac rehospitalization (p=0.003). Only -866 G/G individuals had a reduction in cardiac rehospitalization with discharge BB (G/G HR 0.09, p=0.05 vs. G/A-A/A HR 2.63, p=0.23).
Conclusions: This is the first pharmacogenetic study to our knowledge involving UCP2. Our results suggest variable response to common post-ACS medications among UCP2 -866G>A and Ala55Val individuals. These results could be used in the future to optimize and individualize post-ACS medication regimens in order to improve outcomes.