| RRC ID |
2030
|
| 著者 |
Morita N, Yasumori T, Nakayama K.
|
| タイトル |
Human MDR1 polymorphism: G2677T/A and C3435T have no effect on MDR1 transport activities.
|
| ジャーナル |
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.
|
| 巻・号 |
65(11)
|
| ページ |
1843-52
|
| 公開日 |
2003-6-1
|
| DOI |
10.1016/s0006-2952(03)00178-3
|
| 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 |
4.96
|
| 引用数 |
101
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| 遺伝子材料 |
Human MDR1 cDNA (RDB01372) |
