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Pharmacogenomics J. 2017 Mar;17(2):137-145. doi: 10.1038/tpj.2015.93. Epub 2016 Feb 9.

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Author information

1
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
2
Departments of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
3
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
4
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
5
Children's Hospital Oakland Research Institute, Oakland, CA, USA.
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
7
Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
8
Center for Pharmacogenomics; College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
9
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
10
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
11
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
12
Departments of Pharmacology, Psychiatry, and Human Genetics/Internal Medicine, College of Medicine; Colleges of Pharmacy and Environmental Health Sciences, The Ohio State University, Columbus, OH, USA.
13
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
14
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
15
Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.

Abstract

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-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. 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.

PMID:
26856248
PMCID:
PMC4980276
[Available on 2017-09-01]
DOI:
10.1038/tpj.2015.93
[Indexed for MEDLINE]
Free PMC Article

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