title: Expression levels of the ABCG2 multidrug transporter in human erythrocytes correspond to pharmacologically relevant genetic variations.
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.
authors.affiliation: Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Kasza
authors.forename: György
authors.initials: G
authors.lastname: Várady
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koszarska
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Adrienn
authors.initials: A
authors.lastname: Németh
authors.forename: Gergely
authors.initials: G
authors.lastname: Szakács
authors.forename: Balázs
authors.initials: B
authors.lastname: Sarkadi
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D018389:Codon, Nonsense / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense; D009363:Neoplasm Proteins