Expression Levels of the ABCG2 Multidrug Transporter in Human Erythrocytes Correspond to Pharmacologically Relevant Genetic Variations 英文参考文献.docVIP

ExpressionLevelsoftheABCG2MultidrugTransporterin HumanErythrocytesCorrespondtoPharmacologically RelevantGeneticVariations Ildiko′ Kasza1,2,Gyo¨rgyVa′rady1,2,5,HajnalkaAndrikovics3,MagdalenaKoszarska3,AttilaTordai3, GeorgeL.Scheffer4,AdriennNe′meth2,GergelySzaka′cs5,Bala′zsSarkadi1,3,5* 1 Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary, 2 CellPharma Kft, Budapest, Hungary, 3 Hungarian National Blood Transfusion Service, Budapest, Hungary, 4 Free University Medical Center, Amsterdam, The Netherlands, 5 Institute of Molecular Pharmacology and Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences (HAS), Budapest, Hungary 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. Citation: Kasza I, Va′rady G, Andrikovics H, Koszarska M, Tordai A, et al. (2012) Expression Levels of th