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.