Expression of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in peripheral blood lymphocytes amongst children and young adults

Abstract

Multidrug resistance protein 1 (MDR1, ABCB1 or P-glycoprotein) and multidrug resistance-associated protein 1 (MRP1, ABCC1 or LT C4 transporter) are active membrane-associated efflux transporters with broad substrate specificity. The aim of this study was to assess the physiological expression of these proteins in the peripheral blood lymphocytes (PBLs) and selected polymorphisms in genes for these proteins in healthy children and young adults. The PBLs MDR1 expression in 41 subjects (aged from 2 months to 22.5 years of age) and PBLs MRP1 in 40 subjects (aged from 2 months to 22 years of age) were determined by using a flow cytometry analysis with the indirect immunofluorescence staining technique. Genotyping of rs1045642 (C3435T) and rs3213619 (T-129C) single nucleotide polymorphisms (SNPs) in ABCB1 gene and rs45511401 (G671V) SNP in ABCC1 gene was performed with TaqMan probes and by direct sequencing. We found a statistically significant dependence of PBLs MDR1 (but not PBLs MRP1) expression on age (Spearman R = -0.40014, p = 0.0095). The increased PBLs MDR1 expression was found in children up to 1 year of age and from 4 to 6 years of calendar age. In addition, this increased expression may reduce the concentration of MDR1-transported immunomodulatory and antiviral drugs in lymphocytes and thus lead to the attenuated efficacy of these drugs in younger children. The impact of selected gene polymorphisms on the expression was not found.