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Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes
Author(s) -
Flegel Willy Albert,
Srivastava Kshitij,
Sissung Tristan Michael,
Goldspiel Barry Ronald,
Figg William Douglas
Publication year - 2021
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12999
Subject(s) - pharmacogenomics , atp binding cassette transporter , abcg2 , biology , gene , drug metabolism , transporter , multidrug resistance associated proteins , solute carrier family , drug , pharmacology , genetics
The PharmacoScan pharmacogenomics platform screens for variation in genes that affect drug absorption, distribution, metabolism, elimination, immune adverse reactions and targets. Among the 1,191 genes tested on the platform, 12 genes are expressed in the red cell membrane: ABCC1 , ABCC4 , ABCC5 , ABCG2 , CFTR , SLC16A1 , SLC19A1 , SLC29A1 , ATP7A , CYP4F3 , EPHX1 and FLOT1 . These genes represent 5 ATP‐binding cassette proteins, 3 solute carrier proteins, 1 ATP transport protein and 3 genes associated with drug metabolism and adverse drug reactions. Only ABCG2 and SLC29A1 encode blood group systems, JR and AUG, respectively. We propose red cells as an ex vivo model system to study the effect of heritable variants in genes encoding the transport proteins on the pharmacokinetics of drugs. Altered pharmacodynamics in red cells could also cause adverse reactions, such as haemolysis, hitherto unexplained by other mechanisms.