ABCB1基因多态性与非霍奇金淋巴瘤患者甲氨蝶呤毒副反应关系研究
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- 英文论文题名：Relationships between ABCB1 genetic polymorphisms and toxicities of methotrexate in patients with non-Hodgkin's malignant lymphoma
- 论文作者：杨琳 ; 谢瑞祥 ; 吴晖 ; 陈英 ; 陈宁斌
- 英文论文作者：YANG Lin ; XIE Rie-xiang ; WU Hui ; CHEN Ying ; CHEN Ning-bin ; Department of Pharmacy ; Fujian Provincial Cancer Hospital ; Teaching Hospital of Fujian Medical University ; Department of Medicine ; Fujian Provincial Cancer Hospital ; Teaching Hospital of Fujian Medical University
- 年：2016
- 作者机构：福建医科大学教学医院福建省肿瘤医院药剂科;福建省肿瘤医院内科;
- 论文关键词：非霍奇金淋巴瘤 ; 甲氨蝶吟 ; 多药耐药基因1 ; 基因多态性 ; 毒副反应
- 英文论文关键词：NHL ; MTX ; ABCB1 ; genetic polymorphism ; toxicity
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：中文
- 分类号：R733.1
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：5
- 文件大小：330k
- 原文格式：O
- 会议级别：全国
摘要
目的:研究多药耐药基因1(ABCB1)rs1045642基因多态性与非霍奇金淋巴瘤(NHL)患者甲氨蝶呤(MTX)毒副反应关系。方法:收集81例使用大剂量MTX化疗的NHL患者血样,应用直接测序法检测ABCB1 rs1045642基因多态性,根据NCI-CTCAE统一评价MTX化疗后的毒副反应,用SPSS分析基因多态性与MTX毒副反应的关系。结果:CC、CT和TT基因的分布频率分别为43.21%、39.51%和17.28%;C和T等位基因的分布频率为62.96%和37.04%;突变型(CT+TT)患者发生2级以上血小板减少的比例显著高于野生型(CC)患者(P=0.002)。结论:ABCB1rs1045642基因多态性可能影响NHL患者MTX化疗后2级以上血小板减少的发生率。
OBJECTIVE:To investigate the relationships between multi-drug resistance 1(ABCB1) rs1045642 genetic polymorphisms and toxicities of methotrexate in patients with non-Hodgkin's malignant lymphoma(NHL).METHODS:81blood samples were obtained from patients with NHL using high-dose MTX.The genetic polymorphisms of ABCBl rs 1045642 were detected by gene sequencing.The toxicities were evaluated by NCI common terminology criteria for adverse event.The relationships between genetic polymorphisms and toxicities were analysed by SPSS.RESULTS:Frequencies of CC、 CT and TT genotypes were 43.21%、 39.51%and 17.28%;the frequencies of C and T alleles were 62.96%and 37.04%.The rates of thrombocytopenia(≥grade 2) were higher with mutant genotype(CT+TT) carriers compared with wild genotype(CC)(P=0.002).CONCLUSION:The genetic polymorphisms of ABCBl rsl045642 may contribute to the rate of thrombocytopenia(≥grade 2) induced by methotrexate in patients with NHL.
OBJECTIVE:To investigate the relationships between multi-drug resistance 1(ABCB1) rs1045642 genetic polymorphisms and toxicities of methotrexate in patients with non-Hodgkin's malignant lymphoma(NHL).METHODS:81blood samples were obtained from patients with NHL using high-dose MTX.The genetic polymorphisms of ABCBl rs 1045642 were detected by gene sequencing.The toxicities were evaluated by NCI common terminology criteria for adverse event.The relationships between genetic polymorphisms and toxicities were analysed by SPSS.RESULTS:Frequencies of CC、 CT and TT genotypes were 43.21%、 39.51%and 17.28%;the frequencies of C and T alleles were 62.96%and 37.04%.The rates of thrombocytopenia(≥grade 2) were higher with mutant genotype(CT+TT) carriers compared with wild genotype(CC)(P=0.002).CONCLUSION:The genetic polymorphisms of ABCBl rsl045642 may contribute to the rate of thrombocytopenia(≥grade 2) induced by methotrexate in patients with NHL.
引文
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[11]Takatori R,Takahashi KA,Tokunaga D,et al.ABCBl C3435T polymorphism influences methotrexate sensitivity in rheumatioid arthritis patients[J].Clin Exp Rheumatol,2006,24(5):546-554
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[13]陆爱东,张乐萍,王彬等.转运蛋白基因多态性对儿童急性淋巴细胞白血病大剂量甲氨蝶呤治疗的影响[J].临床儿科杂志,2013,31(8):733-736.
[14]Hamidovic A,Hahn K,Kolesar J.Clinical significance of ABCB1 genotyping in oncology[J].J Oncol Pharma Pract,2010,16(1):39-44.
[15]Nersting J.Schmiegelow K.Pharmacogenomics of methotrexate:moving towards individualized therapy[J].Pharmacogenomics,2009,10(12):1887-1889.
[2]魏盈盈,焦溦溦,程思,等.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度与不良反应的相关性[J].中国医院药学杂志,2014,34(22):1915-1918.
[3]韦润红,赵国兴,陈疏敏.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病耐受性临床研究[J].儿科药学杂志,2006,12(3):12-14.
[4]Sadee W.Dai z.Pharmacogenetics/genomics and personalized medicine[J].Hum Mol Genet,2005,14(2):207-214.
[5]Szakacs G,Varadi A,Ozvegy-Laczka C,et al.The role of ABC transporters in drug absorption,distribution,metabolism,excretion and toxicity(ADME-Tox)[J].Drug Discov Today,2008,13(9-10):379-393.
[6]Hooijberg JH,Broxterman HJ,Kool M,et al.Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2[J].Cancer Res,1999,59(l1):2532-2535.
[7]Kolve ME,Fischbach W,Wilhelm M.Primary gastric non-Hodgkin's lymphoma:requirements for diagnosis and staging[J].Recent Results Cancer Res,2000,156:63-68.
[8]Kimchi-Sarfaty C,Oh JM.Kim IW,et al.A"silent"polymorphism in the MDR1 gene changes substrate specificity[J].Science,2007,315(5811):525-528.
[9]Amin ML.P-glycoprotein Inhibition for Optimal Drug Delivery.Drug Target Insights[J],2013,7:27-34
[10]Jamroziak K,Balcerczak E,Smolewski P,et al.MDRl(ABCBl)gene polymorphism C3435T is associated with P-glycoprotein activity in B-cell chronic lymphocytic leukemia[J].Pharmacol Rep,2006,58(5):720-728
[11]Takatori R,Takahashi KA,Tokunaga D,et al.ABCBl C3435T polymorphism influences methotrexate sensitivity in rheumatioid arthritis patients[J].Clin Exp Rheumatol,2006,24(5):546-554
[12]Bohanec Grabar P,Logar D,Lestan B,et al.Genetic determinants of genetic determinants of methotrexate toxicity in rheumatoid arthritis patients:a study of polymorphisms affecting methotrexate transport and folate metabolism[J].Eur J ClinPharmacol,2008,64(11):1057-1068.
[13]陆爱东,张乐萍,王彬等.转运蛋白基因多态性对儿童急性淋巴细胞白血病大剂量甲氨蝶呤治疗的影响[J].临床儿科杂志,2013,31(8):733-736.
[14]Hamidovic A,Hahn K,Kolesar J.Clinical significance of ABCB1 genotyping in oncology[J].J Oncol Pharma Pract,2010,16(1):39-44.
[15]Nersting J.Schmiegelow K.Pharmacogenomics of methotrexate:moving towards individualized therapy[J].Pharmacogenomics,2009,10(12):1887-1889.
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