Expression Levels of the ABCG2 Multidrug Transporter in Human Erythrocytes Correspond to Pharmacologically Relevant Genetic Variations

Ildikó Kasza, György Várady, H. Andrikovics, Magdalena Koszarska, A. Tordai, George L. Scheffer, Adrienn Németh, G. Szakács, B. Sarkadi

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Article numbere48423
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - Nov 15 2012

Fingerprint

membrane proteins
transporters
Membrane Proteins
erythrocytes
Erythrocytes
genetic variation
Erythrocyte Membrane
Proteins
protein synthesis
nonsense mutation
Drug therapy
Pharmacokinetics
Flow cytometry
Nonsense Codon
drug resistance
Biomarkers
uric acid
Uric Acid
Polymorphism
Drug Resistance

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Expression Levels of the ABCG2 Multidrug Transporter in Human Erythrocytes Correspond to Pharmacologically Relevant Genetic Variations. / Kasza, Ildikó; Várady, György; Andrikovics, H.; Koszarska, Magdalena; Tordai, A.; Scheffer, George L.; Németh, Adrienn; Szakács, G.; Sarkadi, B.

In: PLoS One, Vol. 7, No. 11, e48423, 15.11.2012.

Research output: Contribution to journalArticle

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AU - Tordai, A.

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