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目的评价急性淋巴细胞白血病(ALL)患儿CYP3A4*18B基因型对甲氨蝶呤(MTX)血清浓度的影响。方法用限制性片段长度多态性(PCR-RFLP)方法分析91例ALL患儿CYP3A4*18B基因型,用荧光偏振免疫法(FPIA)测定MTX血清浓度。结果GG、GA和AA基因型的分布频率分别为61.54%,30.77%,7.69%;G和A等位基因的分布频率分别为76.92%,23.08%,符合Hardy-Weinberg平衡。GG、GA基因型ALL患儿的24 h和42 h MTX C/D比值相近,AA基因型个体的24 h MTX C/D比值低于GG、GA基因型个体,42 h MTX C/D比值高于GG、GA基因型个体,上述差异均无统计学意义(P>0.05)。结论 CYP3A4*18B基因多态性与MTX剂量调整的血清浓度无显著相关性。
Objective To evaluate the effects of CYP3A4 * 18B genotype on methotrexate (MTX) serum concentration in children with acute lymphoblastic leukemia (ALL). Methods The genotypes of CYP3A4 * 18B in 91 children with ALL were analyzed by restriction fragment length polymorphism (PCR-RFLP). The concentration of MTX was determined by fluorescence polarization immunoassay (FPIA). Results The distribution frequencies of GG, GA and AA genotypes were 61.54%, 30.77% and 7.69%, respectively. The distribution frequencies of G and A alleles were 76.92% and 23.08%, respectively, which were consistent with Hardy-Weinberg equilibrium. The MTX C / D ratios of 24 h and 42 h were similar in children with GG and GA genotypes. The 24 h MTX C / D ratio of AA genotype individuals was lower than that of GG and GA genotypes and the MTX C / D ratio was 42 h In GG, GA genotype individuals, the above differences were not statistically significant (P> 0.05). Conclusion There is no significant correlation between CYP3A4 * 18B polymorphism and MTX dose-adjusted serum concentration.