中华检验医学杂志
中華檢驗醫學雜誌
중화검험의학잡지
CHINESE JOURNAL OF LABORATORY MEDICINE
2014年
1期
60-65
,共6页
刘思婷%李晓蕾%张永%仇锦春%廖清船
劉思婷%李曉蕾%張永%仇錦春%廖清船
류사정%리효뢰%장영%구금춘%료청선
有机阴离子转运子%甲氨蝶呤%前体细胞淋巴母细胞白血病淋巴瘤%P糖蛋白%多药耐药相关蛋白质类%多态性,单核苷酸
有機陰離子轉運子%甲氨蝶呤%前體細胞淋巴母細胞白血病淋巴瘤%P糖蛋白%多藥耐藥相關蛋白質類%多態性,單覈苷痠
유궤음리자전운자%갑안접령%전체세포림파모세포백혈병림파류%P당단백%다약내약상관단백질류%다태성,단핵감산
Organic anion transporters%Methotrexate%Precursor cell lymphoblastic leukemia-lymphoma%P-Glycoprotein%Multidrug resistance-associated proteins%Polymorphism,single nucleotide
目的 探讨三磷酸腺苷结合盒转运体B1(ABCB1)、三磷酸腺苷结合盒转运体C2(ABCC2)和溶质转运蛋白1B1(SLCO1B1)基因多态性与急性淋巴细胞白血病(ALL)患儿大剂量甲氨蝶呤(MTX)化疗毒性作用的相关性.方法 病例对照研究.收集2005年9月至2011年12月南京医科大学附属南京儿童医院142例ALL患儿外周血,采用均相酶放大免疫分析法(EMIT)测定MTX血药浓度,采用聚合酶链反应-连接酶检测(PCR-LDR)技术对ABCB1 、ABCC2和SLCO1B1基因单核苷酸多态性(SNPs)进行基因分型.结果 MTX存在排泄延迟时,其毒性作用发生风险显著增加(OR =2.828,95％ CI:1.217～6.571,P ＜0.05),SLCO1 B1基因rs4149081和rs11045879位点存在强连锁不平衡(R2 =0.979,P＜0.05).多因素分析显示,SLCO1 B1基因rs4149081AA或rs11045879 CC基因型患儿MTX化疗后易出现排泄延迟(OR =4.41,95％CI:1.537 ～ 12.654,P＝0.042),且发生MTX毒性作用的风险显著高于其他基因型患儿(OR =4.118,95％CI:1.135 ～ 14.944,P＝0.022).未发现其他SNPs与MTX排泄延迟或毒性作用的相关性.结论 SLCO1B1基因rs4149081 AA或rs11045879 CC基因型可能是MTX毒性作用的危险因素.
目的 探討三燐痠腺苷結閤盒轉運體B1(ABCB1)、三燐痠腺苷結閤盒轉運體C2(ABCC2)和溶質轉運蛋白1B1(SLCO1B1)基因多態性與急性淋巴細胞白血病(ALL)患兒大劑量甲氨蝶呤(MTX)化療毒性作用的相關性.方法 病例對照研究.收集2005年9月至2011年12月南京醫科大學附屬南京兒童醫院142例ALL患兒外週血,採用均相酶放大免疫分析法(EMIT)測定MTX血藥濃度,採用聚閤酶鏈反應-連接酶檢測(PCR-LDR)技術對ABCB1 、ABCC2和SLCO1B1基因單覈苷痠多態性(SNPs)進行基因分型.結果 MTX存在排洩延遲時,其毒性作用髮生風險顯著增加(OR =2.828,95％ CI:1.217～6.571,P ＜0.05),SLCO1 B1基因rs4149081和rs11045879位點存在彊連鎖不平衡(R2 =0.979,P＜0.05).多因素分析顯示,SLCO1 B1基因rs4149081AA或rs11045879 CC基因型患兒MTX化療後易齣現排洩延遲(OR =4.41,95％CI:1.537 ～ 12.654,P＝0.042),且髮生MTX毒性作用的風險顯著高于其他基因型患兒(OR =4.118,95％CI:1.135 ～ 14.944,P＝0.022).未髮現其他SNPs與MTX排洩延遲或毒性作用的相關性.結論 SLCO1B1基因rs4149081 AA或rs11045879 CC基因型可能是MTX毒性作用的危險因素.
목적 탐토삼린산선감결합합전운체B1(ABCB1)、삼린산선감결합합전운체C2(ABCC2)화용질전운단백1B1(SLCO1B1)기인다태성여급성림파세포백혈병(ALL)환인대제량갑안접령(MTX)화료독성작용적상관성.방법 병례대조연구.수집2005년9월지2011년12월남경의과대학부속남경인동의원142례ALL환인외주혈,채용균상매방대면역분석법(EMIT)측정MTX혈약농도,채용취합매련반응-련접매검측(PCR-LDR)기술대ABCB1 、ABCC2화SLCO1B1기인단핵감산다태성(SNPs)진행기인분형.결과 MTX존재배설연지시,기독성작용발생풍험현저증가(OR =2.828,95％ CI:1.217～6.571,P ＜0.05),SLCO1 B1기인rs4149081화rs11045879위점존재강련쇄불평형(R2 =0.979,P＜0.05).다인소분석현시,SLCO1 B1기인rs4149081AA혹rs11045879 CC기인형환인MTX화료후역출현배설연지(OR =4.41,95％CI:1.537 ～ 12.654,P＝0.042),차발생MTX독성작용적풍험현저고우기타기인형환인(OR =4.118,95％CI:1.135 ～ 14.944,P＝0.022).미발현기타SNPs여MTX배설연지혹독성작용적상관성.결론 SLCO1B1기인rs4149081 AA혹rs11045879 CC기인형가능시MTX독성작용적위험인소.
Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.
