TY - JOUR
T1 - Pharmacogenomics with red cells
T2 - a model to study protein variants of drug transporter genes
AU - Flegel, Willy Albert
AU - Srivastava, Kshitij
AU - Sissung, Tristan Michael
AU - Goldspiel, Barry Ronald
AU - Figg, William Douglas
N1 - Publisher Copyright:
© Published 2020. This article is a U.S. Government work and is in the public domain in the USA
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - DMET
KW - PharmacoScan
KW - drug transporters
KW - erythrocytes
KW - pharmacogenetics
KW - pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=85091731541&partnerID=8YFLogxK
U2 - 10.1111/vox.12999
DO - 10.1111/vox.12999
M3 - Review article
C2 - 32996603
AN - SCOPUS:85091731541
SN - 0042-9007
VL - 116
SP - 141
EP - 154
JO - Vox Sanguinis
JF - Vox Sanguinis
IS - 2
ER -