Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
Variation in the expression level and activity of genes involved in drug disposition and action (“pharmacogenes”) can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-seq to determine the expression levels and alternative splicing of 389 PGRN pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines (LCLs), which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from different individuals across the 5 tissues (N = 139 samples) revealed substantial variation in both expression levels and splicing across samples and tissue types. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use. Overall design: mRNA profile of 389 genes in 24 liver, 20 kidney (cortex), 25 heart (left ventricle), 25 adipose (subcutaneous) samples, and 45 lymphoblastoid cell lines (LCLs). The raw data for the LCL Samples will be available through dbGap under phs000481.
External Link: /pubmed:26856248