【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。更多还原

【Abstract】 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 concentrations 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 polymorphisms. Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX at the time of 24 h and 42 h.Results There were similar frequencies of genotypes and alleles at CYP2C19* 2 and CYP2C19 * 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 differences in the dose- adjusted serum concentration( C /D ratio) of MTX at the 24 h and 42 h among respective genotype groups at CYP2C19*2 and CYP2C19* 3. Conclusion CYP2C19 * 2 and CYP2C19 * 3polymorphisms are not associated with the risk to develop ALL and serum concentrations of MTX.更多还原