Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia.

OBJECTIVE The present study aims to investigate the correlation of polymorphisms of SLCO1B1 gene with the toxicity during therapy with the high-dose methotrexate (MTX) chemotherapy in childhood acute lymphoblastic leukemia. METHODS We analyzed 2 polymorphisms (rs4149081 and rs11045897) in SLCO1B1 gene in 280 Chinese pediatric B-ALL patients, using MTX plasma concentration as an objective and quantifiable marker of toxicity. We utilized Enzyme-multiplied immunoassay technique (EMIT) to measure the plasma concentration of MTX. The polymerase chain reaction-allele specific (PCR-AS) method was utilized to perform the genotyping. RESULTS We found there was a statistically significant association between MTX plasma concentration and the SLCO1B1 rs11045879 CC genotype (P<0.05). We also found the rs4149081 AA genotype was associated with high-MTX plasma concentrations. A-C haplotype carriers have a higher risk for MTX delayed clearance but G-T haplotype was associated with a lower risk for MTX delayed clearance. CONCLUSIONS The rs4149081 AA genotype and the rs11045897 CC genotype could be indicators for high-MTX plasma concentrations in children with ALL.