Abstract 16477: Genomics of Response to Statins: An Electronic Medical Record-Based Genome-Wide Association Study
Introduction: The response to HMG-CoA reductase inhibitors (statins)-widely used for reducing the risk of myocardial infarction and stroke by lowering serum cholesterol levels-may be influenced by genetic factors.
Hypothesis: We assessed the hypothesis that genetic variants are associated with response to statin therapy by conducting an electronic medical record (EMR)-based genome-wide association study (GWAS).
Methods: Total cholesterol levels were obtained from the EMR of 3335 patients participating in a GWAS for peripheral arterial disease. Statin use was ascertained using natural language processing (NLP). We identified 1203 patients with two sets of fasting lipid profiles before initiation and between weeks 4-8 of statin therapy. Patients were excluded if they were on any other lipid-lowering drugs during this time period or had <10 % decrease in total cholesterol levels (suggesting nonadherence). Patients on statins other than simvastatin were normalized to equivalent dose of simvastatin: 10 mg of simvastatin equaled 1.25, 5, 20, 20 and 40 mg of rosuvastatin, atorvastatin, pravastatin, lovastatin and fluvastatin respectively. Genetic association analysis was performed using PLINK in 646 patients with ≥ 10 % of total cholesterol decrease from baseline, adjusting for age, sex, baseline cholesterol levels and statin dose.
Conclusion: The top two SNPs associated with statin response are shown in Table 1. The variant rs2869961 is in the 5’ flanking region of CEBPB, a transcription factor that regulates expression of apolipoprotein A which plays a significant role in adipogenesis, glucose and lipid metabolism. Our study demonstrates the potential utility of EMR for pharmacogenetic studies. We plan to replicate our finding in additional samples from various sites in the electronic MEdical Record and GEnomics (eMERGE) network (n=~17,000).
- © 2011 by American Heart Association, Inc.