RGD Reference Report - Association of ABCC2 -24C>T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. - Rat Genome Database

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Association of ABCC2 -24C>T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia.

Authors: Liu, Y  Yin, Y  Sheng, Q  Lu, X  Wang, F  Lin, Z  Tian, H  Xu, A  Zhang, J 
Citation: Liu Y, etal., PLoS One. 2014 Jan 3;9(1):e82681. doi: 10.1371/journal.pone.0082681. eCollection 2014.
RGD ID: 11080959
Pubmed: PMID:24404132   (View Abstract at PubMed)
PMCID: PMC3880259   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0082681   (Journal Full-text)

Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The ABCC2 -24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 -24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the -24T allele in ABCC2 gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The -24T allele in ABCC2 gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the -24T allele in ABCC2 gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute lymphoblastic leukemia treatmentIAGP 11080959DNA:SNP:5'UTR:rs717620(human)RGD 
acute lymphoblastic leukemia treatmentISOABCC2 (Homo sapiens)11080959; 11080959DNA:SNP:5'UTR:rs717620(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc2  (ATP binding cassette subfamily C member 2)

Genes (Mus musculus)
Abcc2  (ATP-binding cassette, sub-family member 2)

Genes (Homo sapiens)
ABCC2  (ATP binding cassette subfamily C member 2)


Additional Information