Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death

• Type of Material: Article
• Authors: Jinhee Kim, Georgia Institute of Technology; Nima Ghasemzadeh, Emory University; Danny Eapen, Emory University; Neo Christopher Chung, Princeton University; John D Storey, Princeton University; Arshed Ali Quyyumi, Emory University; Greg Gibson, Georgia Institute of Technology
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Kim et al.; licensee BioMed Central Ltd.
• Final Published Version (URL): http://genomemedicine.com/content/6/5/40
• Title of Journal or Parent Work: Genome Medicine
• ISSN: 1756-994X
• Volume: 6
• Issue: 5
• Start Page: 40
• End Page: 40
• Grant/Funding Information: Funding for collection and management of samples was received from the Robert W Woodruff Health Sciences Center Fund, Emory Heart and Vascular Center, Katz Family Foundation Preventive Cardiology Grant and NIH Grant UL1 RR025008 from the Clinical and Translational Science Award program NIH grant R01HL089650.; This work was supported by start-up funding to GG from the Georgia Tech Research Foundation, and by NIH grant P01-GM0996568.; The Emory Cardiovascular Biobank is supported by the Emory Clinical Cardiovascular Research Institute (ECCRI) for recruitment of participants, compilation of data, and preparation of samples.
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, General

Abstract

Background Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death. Methods Peripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death. Results In both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates. Conclusions A specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.