Expression Levels of the ABCG2 Multidrug Transporter in Human Erythrocytes Correspond to Pharmacologically Relevant Genetic Variations
Open Access
- 15 November 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (11), e48423
- https://doi.org/10.1371/journal.pone.0048423
Abstract
We have developed a rapid, simple and reliable, antibody-based flow cytometry assay for the quantitative determination of membrane proteins in human erythrocytes. Our method reveals significant differences between the expression levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic variant. Moreover, we find that nonsense mutations on one allele result in a 50% reduction in the erythrocyte expression of this protein. Since ABCG2 polymorphisms are known to modify essential pharmacokinetic parameters, uric acid metabolism and cancer drug resistance, a direct determination of the erythrocyte membrane ABCG2 protein expression may provide valuable information for assessing these conditions or for devising drug treatments. Our findings suggest that erythrocyte membrane protein levels may reflect genotype-dependent tissue expression patterns. Extension of this methodology to other disease-related or pharmacologically important membrane proteins may yield new protein biomarkers for personalized diagnostics.Keywords
This publication has 51 references indexed in Scilit:
- Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system JuniorNature Genetics, 2012
- Decreased extra-renal urate excretion is a common cause of hyperuricemiaNature Communications, 2012
- Gout, genetics and ABC transportersF1000 Biology Reports, 2011
- Multiple Genetic Loci Influence Serum Urate Levels and Their Relationship With Gout and Cardiovascular Disease Risk FactorsCirculation: Cardiovascular Genetics, 2010
- Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic DiagnosisAdvances in Pharmacological Sciences, 2010
- Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti‐cancer effects and pharmacological propertiesBritish Journal of Pharmacology, 2009
- Major SNP (Q141K) Variant of Human ABC Transporter ABCG2 Undergoes Lysosomal and Proteasomal DegradationsPharmaceutical Research, 2008
- Interaction with the 5D3 Monoclonal Antibody Is Regulated by Intramolecular Rearrangements but Not by Covalent Dimer Formation of the Human ABCG2 Multidrug TransporterPublished by Elsevier BV ,2008
- Genetic Variation in Efflux Transporters Influences Outcome to Methotrexate Therapy in Patients with PsoriasisJournal of Investigative Dermatology, 2008
- Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levelsBlood, 2005