CYP2C19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  

Associations between CYP2C19 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7期577-580,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基金资助项目(2012-C03)

摘　　要：目的考察CYP2C19*2(G681A)和CYP2C19*3(G636A)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名健康对照受试者和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检测CYP2C19*2和CYP2C19*3基因型,用荧光偏振免疫分析法测定24,42 h MTX血清浓度。结果 ALL患儿与健康对照人群的CYP2C19*2和CYP2C19*3基因型与等位基因分布频率相近,与野生等位基因相比,变异等位基因(A)降低了ALL的发病风险,但差异无统计学意义。CYP2C19*2和CYP2C19*3各基因型组的ALL患儿于24,42 h MTX浓度与剂量比值(C/D ratio)比较,差异无统计学意义。结论 CYP2C19*2和CYP2C19*3基因多态性与ALL的发病风险和MTX血清浓度无明显相关性。Objective To investigate the associations between CYP2C19＊2 （G681A） and CYP2C19＊3 （G636A） polymorphisms with the risk to develop acute lymphoblastic leukemia （ ALL ） and serum concentra-tions of methotrexate （ MTX）.Methods Peripheral blood samples were obtained from healthy subjects as control samples （ n=283 ） and children with acute lymphoblastic leukemia （ n =91 ） to extract genome DNA.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of CYP2C19＊2 and CYP2C19＊3 polymor-phisms.Fluorescence polarization immunoassay was employed to deter-mine the serum concentrations of MTX at the time of 24 h and 42 h.Results There were similar frequencies of genotypes and alleles at CYP2 C19＊2 and CYP2 C19＊3 in healthy subjects and ALL children.Compared with wid alleles , variant alleles （ A） lowered the risk of ALL , but there was no statistical difference.There were no significant differ-ences in the dose-adjusted serum concentration （ C/D ratio） of MTX at the 24 h and 42 h among respective genotype groups at CYP2 C19＊2 and CYP2C19＊3.Conclusion CYP2C19＊2 and CYP2C19＊3 polymorphisms are not associated with the risk to develop ALL and serum concentrations of MTX.

关 键 词：急性淋巴细胞白血病 细胞色素P450 2 C19 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]