Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.

Willy Albert Flegel, Kshitij Srivastava, Tristan Michael Sissung, Barry Ronald Goldspiel, William Douglas Figg

Journal: Vox sanguinis 2021;116(2):141-154

PMID: 32996603

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Abstract

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.

Address: Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.; Clinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.; Clinical Trials Operations and Informatics Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

DOI: 10.1111/vox.12999

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MeSH Terms: ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters, Blood Group Antigens, Copper-Transporting ATPases, Cystic Fibrosis Transmembrane Conductance Regulator, Cytochrome P450 Family 4, Epoxide Hydrolases, Equilibrative Nucleoside Transporter 1, Erythrocytes, Humans, Membrane Proteins, Membrane Transport Proteins, Monocarboxylic Acid Transporters, Multidrug Resistance-Associated Proteins, Neoplasm Proteins, Pharmacogenetics, Polymorphism, Genetic, Reduced Folate Carrier Protein, Symporters