CYP3A5基因和MDR1基因位点的单核苷酸多态性与CML细胞遗传学复发风险的关系分析  

Relation between single Nucleotide Polymorphisms of CYP3A5 Gene and MDR1 Gene Loci and Risk of CML Cytogenetic Relapse

作　　者：杨章元[1] 张友山[2] 梁彩霞[2] 周正菊[3] YANG Zhang-Yuan;ZHANG You-Shan;LIANG Cai-Xia;ZHOU Zheng-Ju(Department of Clinical Laboratory,The First People's Hospital of Jingzhou ,City,Jingzhou434000,Hubei Province,China;Department of Hematology,The First People's Hospital of Jingzhou ,City,Jingzhou434000,Hubei Province,China;Blood Tumor Laboratory,The First People's Hospital of Jingzhou ,City,Jingzhou434000,Hubei Province,China)

机构地区：[1]荆州市第一人民医院检验科,湖北荆州434000 [2]荆州市第一人民医院血液科,湖北荆州434000 [3]荆州市第一人民医院血液肿瘤实验室,湖北荆州434000

出　　处：《中国实验血液学杂志》2018年第6期1644-1648,共5页Journal of Experimental Hematology

摘　　要：目的:分析CYP3A5基因和MDR1基因位点的单核苷酸多态性(SNP)与慢性髓系白血病(CML)细胞遗传学复发风险的关系。方法:收集本院收治的90例行伊马替尼治疗的CML患者的临床资料,根据有无复发进行分组,并分析CYP3A5基因和MDR1基因位点的SNP与CML细胞遗传学复发风险的关系。结果:无细胞遗传学复发者41例(无复发组),复发者49例(复发组),随访36个月。相比MDR1基因位点中的C3435T、C1236T的TT+CT基因型的患者,CC基因型的患者细胞遗传学复发的几率显著升高(P <0. 05)。相比MDR1基因位点中的C3435T的CT+CC基因型的患者,TT基因型的患者细胞遗传学复发的几率显著下降(P <0. 05)。相比MDR1基因位点中的C1236T、C3435T的CT、CC基因型患者,TT基因型者无复发生存期明显延长(P <0. 05)。相比无复发组,复发组中性粒细胞减少症(29. 27%vs 71. 43%)、血液毒性(39. 02%vs 61. 22%)的发生率显著升高(P <0. 05)。伊马替尼剂量(OR=2. 95,95%CI:1. 37-7. 76)与MDR1基因中的C3435T基因型(OR=0. 09,95%CI:0. 05～0. 72)是CML患者细胞遗传学复发的影响因素(均P <0. 05)。结论:伊马替尼治疗剂量与MDR1基因中的C3435T、C1236T基因型对CML患者细胞遗传学复发造成一定的影响,其中MDR1基因中的C3435T基因型对评估患者细胞遗传学复发风险具有一定的预测价值,因此可作为一种临床潜在的生物标志物。Objective: To analyze the relation between the signle nucleotide polymorphisms ( SNP) of CYP3A5 gene and MDR1 gene loci and the risk of cytogenetic relapse in chronic myeloid leukemia ( CML) .Methods: The clinical data of 90 patients with CML treated with imatinib in our hospital were collected.The patients were divided into 2 groups: non-relapse and relapse according to relapse and non-relapse,then the relation between the SNP of CYP3A5 gene and MRD1 gene loci and the risk of cytogenetic relapse in CML patients.Results: The grouping result showed that the patients with non cytogenetic relapse accounted for 41 cases those were enrolled in non-relapse group,and patient -with cytogenetic relapse accounted for 49 cases those were enrolled in relapse group.The follow-up time was 36 months.The detection showed that the incidence of cytogenetic relapse in the patients with CC genotype was significantly higher than that in the patients with TT + CT genotype of C3435T and C1236T at MDR1 gene loci ( P<0.05) .Compared with the patients with CT + CC genotype in C3435T locus of MDR1 gene,the rate of cytogenetic relapse in the patients with TT genotype decreased significantly ( P<0.05) .Compared with patients with CT + CC phemotype of C3435T in MDR1 gene locus,the non-relapse survival time of TT genotypes was significantly prolonged ( P<0.05) .Compared with nonrelapse group,the incidence of neutropenia ( 29.27% vs 71.43%) and blood toxicity ( 39.02% vs 61.22%) in the relapse group increased significantly ( P<0.05) .The imatinib dose ( OR = 2.95,95% CI: 1.37 ~ 7.76) and the C3435T genotype in MDR1 genes ( OR = 0.09,95% CI: 0.05 ~ 0.72) were the factors affecting the cytogenetic relapse of the patients with CML ( both P<0.05) .Conclusion: The therapeutic dose of imatinib and the C3435T and C1236T genotypes in MDR1 gene have a certain effect on the cytogenetic relapse of CML patients.C3435T genotypes in the MDR1 gene showed a certain predictive value for evaluating the risk of cytogenetic relapse,which can be used as a clinical

关 键 词：慢性髓系白血病 细胞遗传学复发 伊马替尼 CYP3A5基因 MDR1基因 

分 类 号：R733.72[医药卫生—肿瘤]