Getting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell linesJ.M.Hillger, C.Diehl, E.van Spronsen, D.I.Boomsma, P.E.Slagboom, L.H.Heitman, A.P.IJzerman Division of... Show moreGetting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell linesJ.M.Hillger, C.Diehl, E.van Spronsen, D.I.Boomsma, P.E.Slagboom, L.H.Heitman, A.P.IJzerman Division of Medicinal Chemistry, LACDR, Leiden University, The Netherlands Department of Biological Psychology, VU University Amsterdam, The Netherlands Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, The Netherlands Abstract 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 A2A receptor (A2AR) 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 A2AR response in particular and GPCR responses in general. Graphical abstract Show less
