title: Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pediatries, Provincial Hospital Affiliated to Shandong University 324 Jingwu Road, Jinan, Shandong 250021, China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhai
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Qian
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Fudan University No. 399 Wanyuan Road, Shanghai, 201102, P.R. China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhu
keywords: Acute lymphoblastic leukemia; SLCO1B1; methotrexate; toxicity