CYP1A2基因多态性与急性淋巴细胞白血病易感性及甲氨蝶呤血清浓度的关系  

Association among CYP1A2 genetic polymorphisms and the risk to develop acute lymphoblastic leukemia and serum concentrations of methotrexate

作　　者：王淑梅[1] 孙路路[1] 曾蔚欣[1] 章国良[2] 

机构地区：[1]首都医科大学附属北京世纪坛医院药剂科,北京100038 [2]北京大学医学部基础医学院药理学系,北京100191

出　　处：《中国临床药理学杂志》2014年第8期664-666,共3页The Chinese Journal of Clinical Pharmacology

基　　金：首都医科大学附属北京世纪坛医院院级课题基金资助项目(2012-C03)

摘　　要：目的考察CYP1A2*1F(C-163A)基因多态性与急性淋巴细胞白血病(ALL)易感性及甲氨蝶呤(MTX)血清浓度的相关性。方法收集283名健康对照者和91例ALL患儿的外周血,提取基因组DNA。用聚合酶链反应-限制性片断长度多态性法(PCR-RFLP)检测CYP1A2*1F基因型,用荧光偏振免疫分析法(FPIA)测定24,42 h MTX血清浓度。结果健康对照人群和ALL患儿的CYP1A2*1F基因型与等位基因分布符合Hardy-Weinberg平衡,ALL患儿的A等位基因频率(43.41%)显著低于健康对照人群(64.66%)(P<0.01);A等位基因频率的优势比(OR)为0.42,显著降低ALL的发病风险(P<0.0001)。CC、CA和AA基因型组ALL患儿的24,42 h MTX浓度与剂量比值(C/D ratio)差异无统计。结论 CYP1A2*1F可显著降低ALL的发病风险,A等位基因是ALL的保护等位基因,但与MTX血清浓度无显著相关关系。Objective To investigate the association among CYP 1A2＊1F （C-163A） polymorphisms and the risk to develop acute lymphoblas-tic leukemia （ ALL） and serum concentrations of methotrexate.Methods Peripheral blood samples were obtained from healthy subjects （ n=283 ） as control samples and children with ALL （ n =91 ） to extract genome DNA.Polymerase chain reaction -Restriction fragment length polymor-phism （PCR-RFLP） was used to detect the genotypes of CYP 1A2＊1F polymorphisms.Fluorescence polarization immunoassay （ FPIA） was em-ployed to determine the serum concentrations of MTX at the 24 h and 42 h.Results The frequencies of genotypes and alleles at CYP 1A2＊1F in healthy subjects and ALL children met Hardy -Weinberg equilibrium.The frequency of A allele in ALL children （ 43.41%） was significantly lower than that in healthy subjects （64.66%） （P〈0.01）.The odds ra-tio （ OR） of A allele was 0.42 , significantly reducing the risk to develop ALL （ P〈0.0001 ）.There were no significant differences in the dose -adjusted serum concentration （C/D ratio） of MTX at the 24, 42 h among CC, CA and AA genotype groups.Conclusion CYP1A2＊1F signifi-cantly reduces the risk to develop ALL and A allele is a protective allele for ALL.However , there is no significant association between CYP 1 A2＊1 F polymorphism and serum concentrations of MTX in ALL children.

关 键 词：急性淋巴细胞白血病 细胞色素P4501A2 甲氨蝶呤 血清浓度 

分 类 号：R557.4[医药卫生—血液循环系统疾病] R979.1[医药卫生—内科学]