Abstract
Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1), ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia(ALL). Methods This study was designed as a case-control.From September of 2005 to December of 2011，the blood samples were randomly collected from 142 ALL patients from Nanjing Children′s Hospital, Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX, Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503), ABCC2 (rs717620,rs2273697) and SLCO1B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR). Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay （OR=2.828, 95%CI:1.217-6.571，P<0.05).Two SNPs in SLCO1B1, rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other （R2=0.979, P<0.05）.Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay （OR=4.41, 95%CI:1.537-12.654, P=0.042）, and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity （OR=4.118, 95%CI:1.135-14.944, P=0.022）.No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found. Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.(Chin J Lab Med, 2014,37:60-65) Key words: Organic anion transporters; Methotrexate; Precursor cell lymphoblastic leukemia-lymphoma; P-Glycoprotein; Multidrug resistance-associated proteins; Polymorphism, single nucleotide
Published Version
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