In an effort to capture differences in the expression of pharmacogenes between individuals and between tissue types and to characterize novel pharmacogene splice variants, researchers conducted a transcriptomic analysis of 389 pharmacologically important genes in liver, kidney (cortex), heart (left ventricle), and adipose tissue from 139 individuals as well as 45 lymphoblastoid cell lines (LCLs). Tissue samples came from various Pharmacogenomics Reseach Network (PGRN) groups. The list of pharmacogenes was compiled from several sources, including PharmGKB. The results were recently published in The Pharmacogenomics Journal.
The study, “Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines”, reports that many pharmacogenes were highly expressed in liver or kidney when compared to other tissues, although some were consistently expressed at high or low levels in all tissue types, and that many pharmacogenes showed variable expressed when comparing between individuals and tissue types. The authors suspect that some differences in expression between individuals may reflect environmental and health differences between people. Expression of most pharmacogenes was almost always lower in LCLs when compared to the other tissue types that were examined. Finally, the authors report the discovery of several novel pharmacogene splicing events and splice variant differences between tissue types.
These findings suggest that variable expression of pharmacogenes between tissue types and individuals as well as differences in alternative splicing patterns could contribute to the observed variation in drug dosing, response, and toxicities.
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