RRC ID 2030
Author Morita N, Yasumori T, Nakayama K.
Title Human MDR1 polymorphism: G2677T/A and C3435T have no effect on MDR1 transport activities.
Journal Biochem. Pharmacol.
Abstract The two most frequently observed single nucleotide polymorphisms (SNPs) of the human multidrug resistance 1 (MDR1) gene are 2677G/T/A (893Ala/Ser/Thr) and 3435C/T (no amino acid substitution). In this study, six forms of MDR1 cDNAs with the SNPs were expressed in LLC-PK1 cells and their transport activities were determined. Nearly identical amounts of the recombinant MDR1 proteins were expressed in the established cell lines using the Flp recombinase, which integrates a gene of interest at a specific genomic location. Four structurally diverse compounds: verapamil, digoxin, vinblastine and cyclosporin A, were examined for transcellular transport activities and intracellular accumulation. No significant differences were observed between cells expressing five polymorphic types of the MDR1 cDNAs (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) and cells expressing the wild-type (2677G/3435C). These results suggested that the two frequently observed MDR1 SNPs had no effect on the transport activities of MDR1 proteins expressed in LLC-PK1 cells in vitro, and other genetic or environmental factors might control the expression of MDR1 and the in vivo activity of MDR1.
Volume 65(11)
Pages 1843-52
Published 2003-6-1
PII S0006295203001783
PMID 12781336
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Biological Transport Cells, Cultured Genome, Human Genotype* Humans Point Mutation Polymorphism, Single Nucleotide Recombinant Proteins / metabolism
IF 4.581
Times Cited 94
WOS Category PHARMACOLOGY & PHARMACY
Resource
DNA material Human MDR1 cDNA (RDB01372)