7 research outputs found
Incidence of methotrexate (MTX) toxicity by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype.
<p>Incidence of methotrexate (MTX) toxicity by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype.</p
Methotrexate (MTX) plasma concentrations by single nucleotide polymorphism (SNP) genotypes of ATP-binding cassette subfamily C member 2 (<i>ABCC2), ABCC4 and ABCG2</i>.
<p>MTX plasma concentrations were measured at 48<i>ABCC4</i> rs9516519 (<i>A</i>), <i>ABCC4</i> rs868853 (<i>B</i>), <i>ABCC4</i> rs2274407 (<i>C</i>), <i>ABCC2</i> rs3740065 (<i>D</i>), <i>ABCG2</i> rs2231137 (<i>E</i>).</p
Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia
<div><p>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 <i>ABCC2</i> −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the <i>ABCC2</i> −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 <i>−24T</i> allele in <i>ABCC2</i> gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The <i>−24T</i> allele in <i>ABCC2</i> 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 <i>−24T</i> allele in <i>ABCC2</i> 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.</p></div
Association of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype with methotrexate (MTX) toxicity grades.
<p>Association of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype with methotrexate (MTX) toxicity grades.</p
Effects of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype and time on methotrexate (MTX) plasma concentration.
<p>Effects of ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) gene −24C>T genotype and time on methotrexate (MTX) plasma concentration.</p
Methotrexate (MTX) plasma concentrations by ATP-binding cassette subfamily C member 2 (<i>ABCC2</i>) −24C>T polymorphism genotypes.
<p>MTX plasma concentrations were measured at 48<i>ABCC2</i> −24C>T polymorphism genotypes alone (<i>A</i>) or further stratified by gender (<i>B</i>). *<i>p</i><0.05 vs CC.</p