Linked Life Data

16917872

Source:http://linkedlifedata.com/resource/pubmed/id/16917872

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-1
pubmed:abstractText
The human multidrug resistance gene MDR1 encodes the protein product P-glycoprotein (P-gp). P-gp is an integral membrane protein which mediates ATP-dependent substrate efflux. We recently discovered a novel G --> T variant at 1199 nucleotide position of MDR1 which exhibits a 2.3% allelic frequency in leukemia patients. The functional effects of this MDR1-G1199T variant were evaluated with recombinant HEK cells that stably express the wild-type, G1199A, or G1199T variant of the MDR1 protein, P-gp, at comparable levels. A panel of cytotoxic P-gp substrates comprising doxorubicin, vinblastine, vincristine, paclitaxel, or topotecan (a poor P-gp substrate) was used to evaluate the functional impact of G1199 variations. Compared to MDR1(wt), MDR1(G1199A) exhibited an increased resistance to doxorubicin, paclitaxel, vinblastine, and vincristine. In contrast, MDR1(G1199T) reduced resistance to (1/4) that of MDR1(wt) for all drugs except topotecan. Expression of MDR1 exhibits some degree of resistance to topotecan, but 1199 variation has no impact. These data were consistent with the variation in intracellular doxorubicin concentrations measured in MDR1 recombinant cells. Our results suggest that patients with the novel MDR1-G1199T variant may exhibit a lower degree of MDR1 dependent chemoresistance, and those with the G1199A polymorphism may exhibit a higher degree of resistance, compared with MDR1 wild-type patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
(c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2767-77
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A novel MDR1 G1199T variant alters drug resistance and efflux transport activity of P-glycoprotein in recombinant Hek cells.
pubmed:affiliation
Department of Pharmaceutics and Medicine, University of Washington, Seattle, Washington 98195-7610, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural