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

Vox Sang. 2021 Feb;116(2):141-154. doi: 10.1111/vox.12999. Epub 2020 Sep 30.

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.

Keywords: DMET; PharmacoScan; drug transporters; erythrocytes; pharmacogenetics; pharmacogenomics.

Publication types

  • Review

MeSH terms

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

Substances

  • ABCC4 protein, human
  • ABCC5 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Blood Group Antigens
  • CFTR protein, human
  • Equilibrative Nucleoside Transporter 1
  • Membrane Proteins
  • Membrane Transport Proteins
  • Monocarboxylic Acid Transporters
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • SLC29A1 protein, human
  • Symporters
  • flotillins
  • monocarboxylate transport protein 1
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cytochrome P450 Family 4
  • CYP4F3 protein, human
  • Epoxide Hydrolases
  • EPHX1 protein, human
  • ATP7A protein, human
  • Copper-Transporting ATPases
  • multidrug resistance-associated protein 1