Association of ABCB1, ABCC2 and SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy
10.3760/cma.j.issn.1009-9158.2014.01.015
- VernacularTitle:ABCB1和ABCC2及SLCO1B1基因多态性与大剂量甲氨蝶呤化疗毒性作用的相关性
- Author:
Siting LIU
;
Xiaolei LI
;
Yong ZHANG
;
Jinchun QIU
;
Qingchuan LIAO
- Publication Type:Journal Article
- Keywords:
Organic anion transporters;
Methotrexate;
Precursor cell lymphoblastic leukemia-lymphoma;
P-Glycoprotein;
Multidrug resistance-associated proteins;
Polymorphism,single nucleotide
- From:
Chinese Journal of Laboratory Medicine
2014;37(1):60-65
- CountryChina
- Language:Chinese
-
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 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL 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 SLCO1 B1 (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.
