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

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.

Vox sanguinis. 2021;(2):141-154

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.

Methodological quality

Publication Type : Review

Metadata