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The G671V variant of MRP1/ABCC1 links doxorubicin-induced acute cardiac toxicity to disposition of the glutathione conjugate of 4-hydroxy-2-trans-nonenal.

Author
Abstract
:

Doxorubicin-induced acute cardiotoxicity is associated with the Gly671Val (G671V; rs45511401) variant of multidrug resistance-associated protein 1 (MRP1). Doxorubicin redox cycling causes lipid peroxidation and generation of the reactive electrophile, 4-hydroxy-2-trans-nonenal (HNE). Glutathione forms conjugates with HNE, yielding an MRP1 substrate, GS-HNE, whose intracellular accumulation can cause toxicity.

Year of Publication
:
2012
Journal
:
Pharmacogenetics and genomics
Volume
:
22
Issue
:
4
Number of Pages
:
273-84
ISSN Number
:
1744-6872
URL
:
https://doi.org/10.1097/FPC.0b013e328350e270
DOI
:
10.1097/FPC.0b013e328350e270
Short Title
:
Pharmacogenet Genomics
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