GSTT1,GSTM1和NQO1基因多态性与急性髓系白血病发生及其重现染色体异常关系的研究

Relationship between GSTT1, GSTM1 and NQO1 gene polymorphism and acute myeloid leukemia and recurrent chromosome translocations

目的探讨GSTT1,GSTM1和NQO1基因多态性与原发性急性髓系白血病(AML)易感性及AML染色体核型异常的关系。方法228例AML和241名与患者无血缘关系的正常人群对照,用多重聚合酶链反应(PCR)方法检测GSTT1和GSTM1基因型,用PCR限制性内切酶片段长度多态性(RFLP)方法分析NQO1基因型。结果AML患者GSTM1无效型(null)比例(62.3%)明显高于正常对照组(52.7%),而GSTT1无效型(null)比例与正常对照组比较,差异无统计学意义。NQO1C609TC/T和T/T基因型比例AML患者(分别为53.1%和25.0%)、t(8;21)(q22;q22)/AMLETO阳性患者(分别为64.3%和25.0%)、t(15;17)(q22;q11)/PMLRARα阳性患者(分别为57.1%和26.0%)明显高于正常对照组(分别为49.4%和13.7%)。NQO1C609TC/T和T/T基因型患t(8;21)(q22;q22)/AMLETO阳性AML的相对危险性分别为4.487(95%CI:1.282～15.705)和6.293(95%CI:1.536～25.782),NQO1C609TC/T和T/T基因型患t(15;17)(q22;q11)/PMLRARα阳性AML的相对危险性分别为2.531(95%CI:1.286～4.981)和4.149(95%CI:1.856～9.275)。结论NQO1C609TC/T和T/T基因型与我国成人原发性AML,特别是伴重现染色体异常t(8;21)(q22;q22)/AMLETO阳性及t(15;17)(q22;q11)/PMLRARα阳性AML高度相关。

Objective To investigate the impact of GSTM1, GSTT1 and NQO1 genotypes on susceptibility to acute myeloid leukemia （AML） and recurrent chromosome translocations of AML Methods GSTY1, GSTM1 and NQO1 genotypes were detected in 228 adult patients with de novo AML and 241 controls by PCR or PCR-RFLP. Results The frequency of GSTM1 null genotype in the AML patients was 62. 3% , significantly higher than that in the normal controls （52. 7% , P =0. 036） , however, no significant difference was found in the incidence of GSTF1 null genotype. The frequencies of NQO1C609T C/T and T/T genotypes were 53. 1% and 25.0% respectively among the total AML patients （53.1% and 25.0% respectively）, 64. 3% and 25.0% respectively among the AML patients with t （8 ; 21 ） （q22; q22）/AML- ETO fusion gene, and 57. 1% and 26.0% respectively among the AML patient with t （15; 17） （q22; q11）/PML-RARα fusion gene, all significantly higher than those in the controls （49.4% and 13.7% respectively）. The relative risk of t （8 ; 21 ） （ q22 ; q22 ）/AML-ETO （ ＋ ） AML was 4. 487 （95% CI： 1. 282- 15. 705）for the subjects with NQO1C609T C/T genotype, and was 6. 293 （95% CI： 1. 536-25. 782） for the subjects with NQO1C609T T/T genotype. The relative risk of t（ 15;17 ） （q22;q11 ）/PML-RARα （ ＋ ）AML was 2.531 （95% CI：1.286-4.981） for the subjects with NQO1C609T C/T genotype, and was 4. 149（95% CI： 1. 856-9. 275 ） for the subjects with NQO1C609T T/T genotype. Conclusion Determination of the NQO1 C609T genotypes may be used as a stratification marker to predict high-risk individuals for AML, especially for AMLwith t （ 8 ;21 ） （ q22 ;q22 ）/AML-ETO fusion gene and t（ 15 ; 17 ） （ q22 ;q11 ）/PML- RARα fusion gene.