期刊
BIOCHEMICAL PHARMACOLOGY
卷 115, 期 -, 页码 114-122出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2016.06.006
关键词
Label-free; Lymphoblastoid cell lines; G protein-coupled receptors; Adenosine A(2A) receptor; Single Nucleotide Polymorphism; Precision medicine
资金
- Center for Collaborative Genomic Studies on Mental Disorders [NIMH U24 MH068457-06]
Genetic differences between individuals that affect drug action form a challenge in drug therapy. Many drugs target G protein-coupled receptors (GPCRs), and a number of receptor variants have been noted to impact drug efficacy. This, however, has never been addressed in a systematic way, and, hence, we studied real-life genetic variation of receptor function in personalized cell lines. As a showcase we studied adenosine A(2A) receptor (A(2A)R) signaling in lymphoblastoid cell lines (LCLs) derived from a family of four from the Netherlands Twin Register (NTR), using a non-invasive label-free cellular assay. The potency of a partial agonist differed significantly for one individual. Genotype comparison revealed differences in two intron SNPs including rs2236624, which has been associated with caffeine-induced sleep disorders. While further validation is needed to confirm genotype-specific effects, this set-up clearly demonstrated that LCLs are a suitable model system to study genetic influences on A(2A)R response in particular and GPCR responses in general. (C) 2016 Elsevier Inc. All rights reserved.
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