CAJ | 학술논문

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。
목적：고찰CYP1A2*1F（ C-163A）기인다태성여급성림파세포백혈병（ ALL）역감성급갑안접령（ MTX）혈청농도적상관성。방법수집283명건강대조자화91례ALL환인적외주혈，제취기인조DNA。용취합매련반응-한제성편단장도다태성법（PCR-RFLP）검측CYP1A2*1F기인형，용형광편진면역분석법（FPIA）측정24，42 h MTX혈청농도。결과건강대조인군화ALL환인적CYP1A2*1F기인형여등위기인분포부합Hardy-Weinberg평형，ALL환인적A등위기인빈솔（43.41％）현저저우건강대조인군（64.66％）（P＜0.01）；A등위기인빈솔적우세비（OR）위0.42，현저강저ALL적발병풍험（P＜0.0001）。 CC、CA화AA기인형조ALL환인적24，42 h MTX농도여제량비치（ C/D ratio）차이무통계。결론 CYP1A2*1F가현저강저ALL적발병풍험，A등위기인시ALL적보호등위기인，단여MTX혈청농도무현저상관관계。
Objective To investigate the association among CYP 1A2*1F (C-163A) polymorphisms and the risk to develop acute lymphoblas-tic 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 polymor-phism (PCR-RFLP) was used to detect the genotypes of CYP 1A2*1F polymorphisms.Fluorescence polarization immunoassay ( FPIA) was em-ployed to determine the serum concentrations of MTX at the 24 h and 42 h.Results The frequencies of genotypes and alleles at CYP 1A2*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 ra-tio ( 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 signifi-cantly reduces the risk to develop ALL and A allele is a protective allele for ALL.However , there is no significant association between CYP 1 A2*1 F polymorphism and serum concentrations of MTX in ALL children.