Abstract 20437: Gene Expression Profiling Identifies Differentially Expressed Genes in Cardiac Allograft Vasculopathy
BACKGROUND: Coronary angiography is the current gold standard for screening and diagnosis of cardiac allograft vasculopathy (CAV). Given the invasiveness and marginal sensitivity associated with angiography, minimally invasive sensitive biomarkers are needed to identify CAV early. The goal of our study is to determine differentially expressed genes in CAV that may serve as targets for biomarker development.
Methods: Gene expression profiling and transcriptome analysis using Illumina HiSeq 2000, was performed on 23 cardiac transplant recipients (12 severe CAV ISHLT grade 3 and 11 without CAV) who were matched by age, gender, and duration of transplant. Fastqc, Tophat, Samtools, and CuffDiff were utilized for quality control of raw reads, mapping short reads to reference genomes and testing differential expression between healthy subjects and transplant subject, respectively. Pathway analysis to identify molecular pathways that show expression change in transplant recipients was done using ingenuity pathway analysis (IPA).
Results: Average age was 54.6 years, 69% were men, and the average duration of transplant was 8.1 years. We identified 181 genes termed “big movers”, i.e., genes that show at least two-fold change in expression with raw testing. Of these 181 genes, 149 genes are up-regulated and 32 genes are down-regulated in CAV when compared to nonCAV. MDS plot of expressed genes showed clear separation between CAV and nonCAV samples and further separation in CAV clusters by age. Differentially expressed genes and pathways are shown in table 1.
Conclusion: CAV is associated with differential gene expression in multiple pathways associated with the cell cycle and cell signaling. Elucidation of differentially expressed genes and associated pathways may improve our understanding of CAV and identify targets for early detection of CAV. Longitudinal studies are required to assess the prognostic value of these genes.
Author Disclosures: M. Colvin-Adams: None. N. Harcourt: None. Y. Zhang: None. A. Mitchell: None. K. Liao: None. K. Beckman: None.
- © 2014 by American Heart Association, Inc.