伊马替尼药物代谢转运相关基因多态性与CML患者严重血液学不良反应相关性  

The Association of Polymorphisms Drug Metabolism and Transport of Imatinib Related Gene with Severe Hematology Adverse Effects in Chronic Myeloid Leukemia Patients

作　　者：周汶静[1] 王念[1] 林立[1] 巫丽娟[1] 叶远馨[1] ZHOU Wen-Jing;WANG Nian;LIN Li;WU Li-Juan;YE Yuan-Xin(Department of Laboratory Medicine,West China Hospital of Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]四川大学华西医院实验医学科,四川成都610041

出　　处：《中国实验血液学杂志》2025年第2期344-351,共8页Journal of Experimental Hematology

摘　　要：目的:寻找伊马替尼治疗慢性粒细胞白血病患者发生严重血液学不良反应(AEs)的遗传相关危险因素,评价伊马替尼药物代谢与转运途径基因单核苷酸多态性与严重血液学AEs发生风险之间的相关性。方法:纳入172例中国汉族新诊断慢性粒细胞白血病慢性期且使用伊马替尼进行治疗的患者,分为严重血液学AEs组和非严重血液学AEs组,并随访人口学特征及实验室检查结果。应用SNaPshot对纳入对象11个单核苷酸多态性位点进行分型,分析其与严重血液学AEs的相关性。结果:严重血液学AEs组较非严重血液学AEs组具有更高的白细胞数及EOS%(均P<0.05)和更低的血红蛋白、血细胞比容(均P<0.01)。ABCB1基因rs1045642位点的等位基因频率和基因型频率分布在严重血液学AEs组及非严重血液学AEs组间的差异具有统计学意义(均P<0.05)。rs1045642突变等位基因A携带者严重血液学AEs的发生风险增高(OR=2.09,95%CI:1.24-3.55,P=0.005)。NR1I2基因rs3814055基因型在严重血液学AEs组和非严重血液学AEs组的分布差异具有统计学意义(P<0.05)。ABCB1基因rs1045642的加性模型与隐性模型,以及NR1I2基因rs3814055的隐性模型都与严重血液学AEs发生风险增高相关(OR=2.14、3.28、5.54,均P<0.05)。结论:慢性粒细胞白血病慢性期患者诊断时的白细胞数、EOS%、血红蛋白及血细胞比容与严重血液学AEs发生相关。伊马替尼药物代谢与转运途径相关ABCB1基因rs1045642及NR1I2基因rs3814055与伊马替尼治疗慢性粒细胞白血病患者严重血液学AEs相关,可能是潜在的预测严重血液学AEs发生风险的分子标志物。Objective:To screen the genetic risk factors related to severe hematology adverse effects(AEs)in patients with chronic myeloid leukemia(CML)treated with imatinib(IM),and explore the correlation of single nucleotide polymorphisms(SNPs)in IM drug metabolism and transport pathway gene polymorphism with the risk of severe hematology AEs.Methods:172 newly diagnosed Chinese Han patients in CML chronic phase(CML-CP)treated with IM were included and divided into severe hematology AEs group and non-severe hematology AEs group.The demographic characteristics and laboratory test results were compared between the two groups.11 gene SNP sites in the included subjects were genotyped using SNaPshot multiplex SNPs technique.Results:Compared with non-severe hematology AEs group,the severe hematology AEs group had higher white blood cell(WBC)and EOS%(both P<0.05),but lower hemoglobin(Hb)and hematocrit(HCT)(both P<0.01).For rs1045642 of ABCB1 gene,there were significant differences in the distribution of allele frequency and genotype frequency of this loci between severe hematology AEs group and non-severe hematology AEs group(both P<0.05).Carriers of rs1045642 mutation allele A had an increased risk of severe hematology AEs(OR=2.09,95%CI:1.24-3.55,P=0.005).There was a significant difference in the distribution of NR1I2 gene rs3814055 genotype between severe hematology AEs group and non-severe hematology AEs group(P<0.05).The additive model and recessive model of ABCB1 gene rs1045642 and the recessive model of NR1I2 gene rs3814055 were associated with the increased risk of severe hematology AEs(OR=2.14,3.28,5.54,all P<0.05).Conclusion:Peripheral blood WBC,EOS%,Hb and HCT in patients with newly diagnosed CML-CP are all related to the risk of severe hematology AEs.ABCB1 gene rs1045642 and NR1I2 gene rs3814055 related to the metabolism and transport pathway of IM are associated with severe hematology AEs after IM treatment in CML-CP patients,and they may be potential molecular markers to predict the risk of severe hematology AEs of CM

关 键 词：伊马替尼 慢性粒细胞白血病 严重血液学不良反应 药物代谢动力学 单核苷酸多态性 

分 类 号：R733.72[医药卫生—肿瘤]