细胞色素P450 2E1基因多态性与急性淋巴细胞白血病易感性及其与甲氨蝶呤血清浓度关系探讨  

Associations between cytochrome P450 2E1 genetic polymorphisms with 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9期773-775,779,共4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CYP2E1*5B(G-1293C)和CYP2E1*6(T7632A)基因多态性与急性淋巴细胞白血病(ALL)易感性及其与甲氨蝶呤(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DNA。用聚合酶链反应-限制性片断长度多态性法(PCR-RFLP)检测CYP2E1*5B和CYP2E1*6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 ALL患儿的C(*5B)等位基因频率(24.73%)显著高于健康对照人群(17.31%)(P<0.05);C等位基因频率的优势比(OR)为1.57,C等位基因显著增加ALL的发病风险(P<0.05)。ALL患儿与健康对照人群的CYP2E1*6的基因型与等位基因分布频率相近,CYP2E1*6与ALL的发病风险无显著相关关系。CYP2E1*5B和CYP2E1*6各基因型组ALL患儿的24,42 h MTX浓度与剂量比值(C/D ratio)没有显著差异。结论 CYP2E1*5B可显著增加ALL的发病风险,但CYP2E1*6与ALL的发生无关;C等位基因是ALL的易感等位基因,两者的基因多态性与MTX血清浓度无显著相关关系。Objective To investigate the relations between CYP2E1＊5B（ G- 1293C） and CYP2E1 ＊ 6（ T7632A） polymorphisms with the risk to develop acute lymphoblastic leukemia（ ALL） and serum concentrations of methotrexate（ MTX）. Methods Peripheral blood samples were obtained from 283 healthy control subjects and 91 children with acute lymphoblastic leukemia to extract genome DNA. Polymerase chain reaction- Restriction fragment length polymorphism（ PCR- RFLP） was used to detect genotypes of CYP2E1 ＊ 5B and CYP2E1 ＊ 6 polymorphisms. Fluorescence polarization immunoassay（ FPIA） was employed to determine the serum concentrations of MTX at the 24 h and 42 h. Results The frequency of C（ ＊ 5B） allele in ALL children（ 24. 73%）was significantly higher than that in healthy subjects（ 17. 31%）（ P〈0. 05）. The odds ratio（ OR） of C allele was 1. 57,significantly increasing the risk to develop ALL（ P〈0. 05）. There were similar frequencies of genotypes and alleles at CYP2E1＊ 6 in healthy subjects and ALL children and the CYP2E1 ＊ 6 polymorphisms were not associated with the risk to develop ALL. There were no significant differences in the dose-adjusted serum concentration（ C /D ratio） of MTX at the 24 h and42 h among respective genotype groups at CYP2E1＊ 5B and CYP2E1＊ 6. Conclusion CYP2E1＊ 5B significantly increases the risk to develop ALL and C allele is a susceptible allele for ALL. However,there are no significant associations between CYP2E1＊ 6 polymorphisms and the risk to develop ALL. CYP2E1＊ 5B and CYP2E1＊ 6 polymorphisms are not associated with serum concentrations of MTX in ALL children.

关 键 词：急性淋巴细胞白血病 细胞色素P450 2E1 甲氨蝶呤 血清浓度 

分 类 号：R968[医药卫生—药理学] R979.12[医药卫生—药学]