SLC22A1和CYP3A5基因多态性与伊马替尼治疗慢性髓性白血病疗效的相关性研究  

Study on the Relationship of SLC22A1 and CYP3A5 Gene Polymorphism with Therapeutic Efficacy of Imatinib for Chronic Myeloid Leukemia

作　　者：邓伟[1] 朱生东[1] 晁荣[1] 董雪梅[1] DENG Wei;ZHU Shengdong;CHAO Rong;DONG Xuemei(Dept.of Pediatric Internal Medicine,Gansu Maternal and Child Health Hospital,Lanzhou 730050,China)

机构地区：[1]甘肃省妇幼保健院小儿综合内科,兰州730050

出　　处：《中国药房》2018年第15期2100-2104,共5页China Pharmacy

基　　金：甘肃省卫生行业科研计划项目(No.GSWSKY-2015-20)

摘　　要：目的:评价SLC22A1(rs628031、rs683369)和细胞色素P450(CYP)3A5(rs776746)基因多态性与伊马替尼治疗慢性髓性白血病的相关性。方法:以"有机阴离子转运体""细胞色素""基因多态性""伊马替尼""慢性粒细胞白血病"及"SLC22A1""CYP3A5"为中文检索词,以"SLC22A1""CYP3A5""Cytochrome""Polymorphism""Imatinib""Chronic myeloid leukemia"为英文检索词,计算机检索Pub Med、Embase、The Cochrane Library、中国生物医学文献数据库、中国知网学术总库、万方数据库、中文科技期刊数据库,收集符合纳入标准的SLC22A1(rs628031、rs683369)和CYP3A5(rs776746)基因多态性与伊马替尼治疗慢性髓性白血病疗效的病例对照研究,检索时限均为从建库起至2018年1月,由两位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后,采用Rev Man 5.3软件对SLC22A1(rs628031、rs683369)和CYP3A5(rs776746)基因多态性与主要分子学反应率(MMR)、完全细胞遗传学反应率(CCy R)的关系进行Meta分析。结果:共纳入13项病例对照研究,合计1 707例患者。Meta分析结果显示,SLC22A1(rs628031)GA+AA基因型患者MMR显著低于GG基因型[OR=0.58,95%CI(0.41,0.83),P<0.01];SLC22A1(rs683369)CG+GG基因型患者MMR显著低于CC基因型[OR=0.64,95%CI(0.42,0.96),P=0.03];CYP3A5(rs776746)AG+GG基因型患者CCy R显著高于AA基因型[OR=2.43,95%CI(1.12,5.27),P=0.02]。结论:SLC22A1和CYP3A5基因多态性可影响伊马替尼对慢性髓性白血病的治疗结局,二者可作为伊马替尼的潜在疗效预测指标。OBJECTIVE:To evaluate the relationship of SLC22A1(rs628031,rs683369)and CYP3A5(rs776746)gene polymorphism with therapeutic efficacy of imatinib for chronic myeloid leukemia(CML).METHODS:Using“organic anion transporter”“cytochrome”“gene polymorphism”“imatinib”“chronic myeloid leukemia”“SLC22A1”“CYP3A5”as chinese retrieval words,“SLC22A1”“CYP3A5”“Polymorphism”“Polymorphism”“Imatinib”“Chronic myeloid leukemia”as english retrieval words,retrieved from PubMed,Embase,The Cochrane Library,CBM,CNKI,Wanfang database and VIP,case-control study on the relationship of SLC22A1(rs628031,rs683369)and CYP3A5(rs776746)gene polymorphism with therapeutic efficacy of imatinib for CML were collected from database establishment to Jan.2018.After literature screening according to inclusion and exclusion criteria,data extraction and quality evaluation by two researchers,Meta-analysis was performed for the relationship of SLC22A1(rs628031,rs683369)and CYP3A5(rs776746)gene polymorphism with main molecules response(MMR)and complete cytogenetics response(CCyR)by using Rev Man 5.3 software.RESULTS:Totally 13 case-control studies were included,involving 1 707 patients.Meta-analysis showed that MMR of SLC22A1(rs628031)GA+AA genotype patients were significantly lower than that of GG genotype patients[OR=0.58,95%CI(0.41,0.83),P<0.01].MMR of SLC22A1(rs683369)CG+GG genotype was significantly lower than CC genotype[OR=0.64,95%CI(0.42,0.96),P=0.03].CCyR of CYP3A5(rs776746)AG+GG genotype was significantly higher than AA genotype[OR=2.43,95%CI(1.12,5.27),P=0.02].CONCLUSIONS:SLC22A1 and CYP3A5 gene polymorphism can influence therapy outcome of imatinib for CML.Both can be used as a potential efficacy predictive indicator of imatinib.

关 键 词：伊马替尼 SLC22A1基因多态性 CYP3A5基因多态性 慢性髓性白血病 相关性研究 

分 类 号：R979.1[医药卫生—药品] R733.7[医药卫生—药学]