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目的 分析生物代谢酶Ⅰ相酶细胞色素P4501A1(CYPIAl)和Ⅱ相酶谷胱甘肽转硫酶GSTM1、GSTT1基因的遗传多态在湖南人群急性白血病患者和健康人群中的分布。方法 采用病例对照研究方法，应用聚合酶链反应及聚合酶链反应-限制性片段长度多态性技术对112例急性淋巴细胞性白血病(ALL)患者和120例急性非淋巴细胞性白血病(ANLL)患者以及204名健康个体的CYP1A1 MspI多态(3801 T-C突变)、GSTM1和GSTT1等基因的多态分布进行分析。结果 ALL组与ANLL组的CYP1A1基因3801位点等位变异的频率分别为74.1%、70.8%，高于对照组(63.3%)，但其差异无统计学意义(P>0.05)；ALL组GSTMl缺失基因型(GSTM1-/-)的频率为60.7%，与对照组(55.4%)比较差异无统计学意义(P>0.05)；ANLL组GSTM1-/-基因型频率为68.3%，与对照组比较差异有统计学意义(P<0.05)。ALL组、ANLL组及对照组的GSTT1缺失基因型(GSTT1-/-)的频率分别为50.9%、55.0%和49.0%，病例组与对照组差异无统计学意义(P>0.05)。GSTM1-/-和GSTT1-/-联合基因型在ALL、ANLL患者组和对照组中的频率分别为33.0%、40.0%和27.5%，其中ANLL组与对照组比较，其差异有统计学意义(P<0.05)。同时携带CYP1A1 Msp I多态突变基因型(杂合突变型或纯合突变型)与GSTM1-/-、GSTT1-/-基因型的个体患ANLL的风险增加(OR=1.890，95%CI：1.084～3.295)。结论 单一的CYP1A1 Msp I多态突变基因型或GSTT1-/-基因型与急性白血病易感性不相关；GSTM1-/-基因型及其与GSTT1-/-基因型、CYP1A1 Msp I多态突变基因型(杂合突变型或纯合突变型)同时存在时增加患ANLL的风险。提示GSTM1-/-可能是ANLL发病的易感因素之一，且与其他缺陷基因型存在协同作用。
Objective To analyze the distribution of genetic polymorphisms of cytochrome P4501A1 (CYPIA1) and GSTT1 gene of glutathione S-transferase (GSTT1) in human leukemia patients and healthy subjects in Hunan Province. Methods A case-control study was conducted in 112 cases of acute lymphoblastic leukemia (ALL) and 120 cases of acute non-lymphocytic leukemia (ANLL) using polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism Patients and 204 healthy individuals CYP1A1 MspI polymorphism (3801 TC mutation), GSTM1 and GSTT1 and other genetic polymorphism distribution analysis. Results The frequency of allelic variation at position 3801 of CYP1A1 gene in ALL group and ANLL group was 74.1% and 70.8% respectively, which was higher than that in control group (63.3%), but there was no significant difference (P> 0.05). The GSTM1 The frequency of GSTM1 - / - genotype was 60.7%, which was not significantly different from that of control group (55.4%) (P> 0.05). The frequency of GSTM1 - / - genotype in ANLL group was 68.3% The difference was statistically significant (P <0.05). The frequency of GSTT1 - deficient genotypes (GSTT1 - / -) in ALL group, ANLL group and control group were 50.9%, 55.0% and 49.0%, respectively. There was no significant difference between the case group and the control group (P> 0.05). The frequencies of GSTM1 - / - and GSTT1 - / - combined genotypes were 33.0%, 40.0% and 27.5% in ALL patients, ANLL patients and controls respectively. There was significant difference between ANLL group and control group P <0.05). Patients with the CYP1A1 Msp I polymorphism (heterozygous mutant or homozygous mutant) and GSTM1 - / -, GSTT1 - / - genotype had an increased risk of ANLL (OR = 1.890, 95% CI: 1.084 ~ 3.295). Conclusion A single genotype of CYP1A1 Msp I polymorphism or GSTT1 - / - genotype is not associated with susceptibility to acute leukemia. GSTM1 - / - genotype and its association with GSTT1 - / - genotype, CYP1A1 Msp I polymorphism (Heterozygous mutant or homozygous mutant) increases the risk of ANLL. It is suggested that GSTM1 - / - may be one of the susceptible factors for the pathogenesis of ANLL, and synergistic with other defective genotypes.