CAJ | 학술논문

目的：考察CYP2E1*5B（G-1293C）和CYP2E1*6（T7632A）基因多态性与急性淋巴细胞白血病（ ALL）易感性及其与甲氨蝶呤（ 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DNA。用聚合酶链反应-限制性片断长度多态性法（PCR-RFLP）检测CYP2E1*5B和CYP2E1*6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 ALL患儿的C（*5B）等位基因频率（24.73％）显著高于健康对照人群（17.31％）（P＜0.05）；C等位基因频率的优势比（OR）为1.57，C等位基因显著增加ALL的发病风险（ P＜0.05）。 ALL患儿与健康对照人群的CYP2E1*6的基因型与等位基因分布频率相近，CYP2E1*6与ALL的发病风险无显著相关关系。 CYP2E1*5B和CYP2E1*6各基因型组ALL患儿的24，42 h MTX浓度与剂量比值（ C/D ratio）没有显著差异。结论 CYP2E1*5B可显著增加ALL的发病风险，但CYP2E1*6与ALL的发生无关；C等位基因是ALL的易感等位基因，两者的基因多态性与MTX血清浓度无显著相关关系。
목적：고찰CYP2E1*5B（G-1293C）화CYP2E1*6（T7632A）기인다태성여급성림파세포백혈병（ ALL）역감성급기여갑안접령（ MTX）혈청농도적상관성。방법수집283명건강대조자화91례ALL환인적외주혈，제취DNA。용취합매련반응-한제성편단장도다태성법（PCR-RFLP）검측CYP2E1*5B화CYP2E1*6기인형，용형광편진면역분석법（ FPIA）측정24，42 h MTX혈청농도。결과 ALL환인적C（*5B）등위기인빈솔（24.73％）현저고우건강대조인군（17.31％）（P＜0.05）；C등위기인빈솔적우세비（OR）위1.57，C등위기인현저증가ALL적발병풍험（ P＜0.05）。 ALL환인여건강대조인군적CYP2E1*6적기인형여등위기인분포빈솔상근，CYP2E1*6여ALL적발병풍험무현저상관관계。 CYP2E1*5B화CYP2E1*6각기인형조ALL환인적24，42 h MTX농도여제량비치（ C/D ratio）몰유현저차이。결론 CYP2E1*5B가현저증가ALL적발병풍험，단CYP2E1*6여ALL적발생무관；C등위기인시ALL적역감등위기인，량자적기인다태성여MTX혈청농도무현저상관관계。
Objective To investigate the relations between CYP 2E1*5B (G-1293C) and CYP2E1*6 ( T7632A) polymorphisms with the risk to develop acute lymphoblastic leukemia ( ALL) and serum concen-trations of methotrexate ( MTX ).Methods Peripheral blood samples were obtained from 283 healthy control subjects and 91 children with a-cute lymphoblastic leukemia to extract genome DNA.Polymerase chain reaction-Restriction fragment length polymorphism ( PCR-RFLP) was used to detect genotypes of CYP2E1*5B and CYP2E1*6 polymor-phisms.Fluorescence polarization immunoassay ( FPIA) was employed to determine the serum concentrations of MTX at the 24 h and 42 h.Re-sults The frequency of C (*5 B ) allele in ALL children ( 24.73%) was significantly higher than that in healthy subjects ( 17.31%) ( P<0.05 ).The odds ratio ( OR) of C allele was 1.57 , significantly increas-ing the risk to develop ALL ( P<0.05 ).There were similar frequencies of genotypes and alleles at CYP2E1*6 in healthy subjects and ALL chil-dren and the CYP2E1*6 polymorphisms were not associated with the risk to develop ALL.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 CYP 2E1*5B and CYP2E1*6.Conclusion CYP2E1*5B significantly in-creases the risk to develop ALL and C allele is a susceptible allele for ALL.However , there are no significant associa-tions between CYP2E1*6 polymorphisms and the risk to develop ALL.CYP2E1*5B and CYP2E1*6 polymorphisms are not associated with serum concentrations of MTX in ALL children.