[CYP3A5基因与MDR1基因位点单核苷酸多态性与慢性粒细胞白血病细胞遗传学复发风险的关系]
[Relation between single Nucleotide Polymorphisms of CYP3A5 Gene and MDR1 Gene Loci and Risk of CML Cytogenetic Relapse].
作者信息
Yang Zhang-Yuan, Zhang You-Shan, Liang Cai-Xia, Zhou Zheng-Ju
机构信息
Department of Clinical Laboratory,The First People's Hospital of Jingzhou City, Jingzhou 434000, Hubei Province, China.
Department of Hematology,The First People's Hospital of Jingzhou City, Jingzhou 434000, Hubei Province, China.
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Dec;26(6):1644-1648. doi: 10.7534/j.issn.1009-2137.2018.06.011.
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 non-relapse 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:1.377.76) and the C3435T genotype in MDR1 genes (OR=0.09, 95% CI:0.050.72) 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 biomarker.
目的
分析细胞色素P450 3A5（CYP3A5）基因和多药耐药基因1（MDR1）基因位点的单核苷酸多态性（SNP）与慢性髓性白血病（CML）细胞遗传学复发风险的关系。
方法
收集我院90例接受伊马替尼治疗的CML患者的临床资料。根据是否复发将患者分为2组：未复发组和复发组，然后分析CYP3A5基因和MDR1基因位点的SNP与CML患者细胞遗传学复发风险的关系。
结果
分组结果显示，细胞遗传学未复发患者41例，纳入未复发组；细胞遗传学复发患者49例，纳入复发组。随访时间为36个月。检测发现，MDR1基因位点C3435T和C1236T的CC基因型患者细胞遗传学复发率显著高于TT + CT基因型患者（P < 0.05）。与MDR1基因C3435T位点CT + CC基因型患者相比，TT基因型患者细胞遗传学复发率显著降低（P < 0.05）。与MDR1基因C3435T位点CT + CC表型患者相比，TT基因型患者的无复发生存时间显著延长（P < 0.05）。与未复发组相比，复发组中性粒细胞减少症（29.27% 对71.43%）和血液毒性（39.02% 对61.22%）发生率显著增加（P < 0.05）。伊马替尼剂量（OR = 2.95，95%CI：1.377.76）和MDR1基因中的C3435T基因型（OR = 0.09，95%CI：0.050.72）是影响CML患者细胞遗传学复发的因素（均P < 0.05）。
结论
伊马替尼治疗剂量及MDR1基因中的C3435T和C1236T基因型对CML患者细胞遗传学复发有一定影响。MDR1基因中的C3435T基因型对评估细胞遗传学复发风险具有一定预测价值，可作为临床生物标志物。
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