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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)141-154
Number of pages14
JournalVox Sanguinis
Volume116
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • DMET
  • PharmacoScan
  • drug transporters
  • erythrocytes
  • pharmacogenetics
  • pharmacogenomics

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