CYP3A5基因多态性及其在急性白血病患者化疗与预后中的意义

©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(ArticleID):1009-2137(2008)01-0026-05CYP3A5,,,,,,,200001(AL)P24503A5(CYP3A5),2(PCR2RFLP)CYP3A533,CYP3A5:88(CYP3A531/31)23(26%),(CYP3A531/33)44(50%),(CYP3A533/33)21(24%)CYP3A53374%,;CYP3A531,3;CYP3A5:(36.619.2)%(7.8912)%(0.50.9)%;(11.62.1)(30.512.2)(52.38.5);(7.51.8)(2715.8)(52.38.1),:CYP3A5,CYP3A5,CYP3A5ALCYP3A5AL;CYP3A5;;R733.71APolymorphismsofCYP3A5GeneinAcuteLeukemiaPatientsandTheirRoleinChemotherapyandPrognosisSHENLi2Jing,CHENFang2Yuan,WANGTing,WANGHai2Rong,ZHONGJi2Hua,HANJie2Ying,OUYANGRen2RongDepartmentofHematology,RenjiHospitalAffiliatedtoJiaotongUniversity,Shanghai200001,ChinaAbstractTheobjectiveofstudywastoinvestigatetheroleofthepolymorphismsandproteinexpressionofCYP3A5geneinthetherapyandprognosisofacuteleukemia(AL)patients,thepolymorphismsofCYP3A5geneandtheexpres2sionofproteinCYP3A5weredetectedbypolymerasechainreaction2restrictionfragmentlengthpolymorphism(PCR2RFLP)andimmunohistochemistrymethodrespectively.TheresultsshowedthattherewerethreeCYP3A5genotypesinthe88cases,namelyCYP3A531/31,CYP3A531/33andCYP3A533/33withfrequenciesof26%,50%and24%,respectively.Therewerenosignificantdifferencesinclinicdatabetweenthethreegroups,buttheexpressionsofCYP3A5ofthreegroupswere(36.619.2)%,(7.89.2)%,(0.50.9)%,theOSwere(11.62.1)months,(30.512.2)months,(52.38.5)months,andtheDFSwere(7.51.8),(2715.8),(52.38.1)months,respectively(p0.05).ItisconcludedthatthepolymorphismofCYP3A5geneisnorelatedwiththemorbidityofAL,butcloselyassociatedwiththeexpressionofCYP3A5inALpatients,andthelatterarecloselyassociatedwiththechemo2therapeuticeffectandprognosis.CYP3A5genotypemaybeusedasanewpredictortothechemotherapeuticeffectandprognosisinALcases.Keywordsacuteleukemia;CYP3A5gene;genepolymorphism;chemotherapyJExpHematol2008;16(1):26-30(AL),,,60%()P450(cytochromeP450,CYPs)3A[1],CYP3A5AL[2],CYP3A533CYP3A5[3]CYP3A[4],CYP3A533,:,30400183:,.:[phone].E2mail:[e-mail]2007-04-01;2007-04-2562JournalofExperimentalHematology2008;16(1):26-30©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(1291),6(123321);49,3988,(AML)71(M212M318M421M518M62);(ALL)15(T3B12);(CML)2M3()As2O3(),DA(+)HA(+)CAG(G2CSF++),ALLDVP(++),,,2006228FAB(OS)(DFS)CYP3A588DNA,PCR2RFLP,CYP3A53AG(CYP3A533),PCR[5],:5’2CTTTAAAGAGCTCTTTT2GTCTCTCA23’,5’2CCAGGAAGCCAGAC2TTTGAT23’25lPCR10PCR2.5l,dNTP0.2mmol/L,0.4mol/L,DNA90ng,TaqDNA1UPTC2100(MJ2Research),955;953055307230,33;725,4PCR25g/L(DY501),DNA/(),PCR8lDde(PromegaProductInformation)10U,371240g/L,(FR2200)200bp,(CYP3A531)1Dde,129bp71bp2;(CYP3A533)1Dde,107bp,22bp71bp3CYP3A5CYP3A5,0.3%H2O230,(0.01mol/L,pH610)9810,CYP3A5(11000,Gentest)4,IgG(1400,SantaCruz)3730,streptavidine2HRP(s2HRP,1400,Dako)3730,(1300mol/L,Dako)3720,s2HRP(1600)3730,PBS0.04%DAB+0.03%H2O210,,,30,,,,CYP3A5,,1000,CYP3A5SPSS11.5,,tKa2plan2MeierDFSLogistic,=0.05CYP3A588,(CYP3A531/31)23(26%);(CYP3A531/33)44(50%);(CYP3A533/33)21(24%)88CYP3A50.137(00.600);3CYP3A5:0.3660.1920.0780.0920.0050.009,3,p0.05,(1234)72CYP3A5©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:471945174119;WBC(109/L)2911195239;0.560.260.350.320.440.32;0.700.200.720.180.680.25p=0.008,,p0.05FAB,CYP3A5,p=0.0649(5),Figure5.CYP3A5genetypeofFABsubgroup.11.81.7(1-115),3,1(CCR1)5(21.7%)14(31.8%)13(61.9%);6(26.1%)7(15.9%)5(23.8%)37,316(69.5%)17(38.7%)4(19%);OS11.62.130.512.252.38.5;DFS7.51.82715.852.38.1p0.1,p0.05(,67),(36),(30),82JExpHematol2008;16(1)©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(n)CYP3A5expressioninBMCCR1(n)Relapse(n)Death(n)OS(month)DFS(month)CYP3A531/31230.3660.192356#16311.62.137.51.83CYP3A531/33440.0780.0923147317330.512.2327.015.83CYP3A533/33210.0050.009135452.38.552.38.1Total880.1360.18231183737.98.233.78.4CCR:continualcompleteremission;OS:overallsurvival;DFS:diseasefreesurvival.#p0.1;3p0.05,comparedwithmutationtypegroupFigure6.DifferenceofOSamongALpatientswithCYP3A5genesubtypes.Figure7.DifferenceofDFSamongALpatientswithCYP3A5genesubtypes.(22),(55,55p=0.005)FAB(p=0.034)(/,p=0.047)WBC(4.0109/L,4.010.0109/L,10.0109/Lp=0.000)CYP3A5(p=0.005)(p=0.008),(p=0.399)(0.5,0.5p=0.46)(0.8,0.8p=0.157),FABCYP3A5CYP3A57q21.1222.1,31.8kb,13,502,,CYP3A(1040)CYP3ACYP3A5(SNP)Jounaidi[6]1996SNP:CYP3A532CYP3A5,2SNP[3],:7GA(CYP3A536)2001Kuehl[3]3AG(CYP3A533)mRNA,CYP3A5CYP3A533CYP3A533SNP,CYP3A5CYP3A5(),CYP3A533:71%-76%;71%-85%;70%;59%-61%;27%-55%;84%-95%;62%-83%[5][7],CYP3A531CYP3A53330%(p=0.026),CYP3A,,88ALCYP3A5,(CYP3A531/31)23(26%);(CYP3A531/33)44(50%);(CYP3A533/33)21(24%),CYP3A53392CYP3A5©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[8],(C0)2(C2),2.3-6.61.4-3.82CYP3A5,CYP3A533AL,3WBC,