【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。更多还原

【Abstract】 Objective To investigate the association among CYP1A2*1F(C- 163A) polymorphisms and the risk to develop acute lymphoblastic 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 polymorphism(PCR- RFLP) was used to detect the genotypes of CYP1A2* 1F polymorphisms. Fluorescence polarization immunoassay(FPIA) was employed to determine the serum concentrations of MTX at the 24 h and 42 h. Results The frequencies of genotypes and alleles at CYP1A2* 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 ratio(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 significantly reduces the risk to develop ALL and A allele is a protective allele for ALL. However,there is no significant association between CYP1A2*1F polymorphism and serum concentrations of MTX in ALL children.更多还原