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1、第四章药物遗传学、药物基因组学与个体化医学药物代谢与遗传因素遗传多态性与药物代谢及分布SNP、基因芯片与药物基因组学PatientResponsetoMedicineVaries“Onesizefitsall?!”“Ihavehypertensionwhichisnotbeingcontrolled.Mydoctorprescribesadrugforhypertension,wewait3-4monthstofindit’snotworkingandthentryanotherone.In18months,I’vetried6newmedicationsandI
2、’mfastlosingconfidenceinthishitormissapproachandinmyphysician”.药物遗传学(pharmacogenetics)一门由药理学和遗传学相互渗透而形成的以研究人体对药物反应的的边缘学科。Anultimategoalofpharmacogeneticsistounderstandhowsomeone'sgeneticmake-updetermineshowwellamedicineworksinhisorherbody,aswellaswhatsideeffectsarelikelytooccur.In1902
3、,BritishphysicianSirGarrodA.suggestedthatgeneticfactorsdirectchemicaltransformationsinhumansandunderlieindividualvariability.In1957,MotulskyA.demonstratedtherelationshipbetweenadversedrugreactionsandgeneticallydeterminedvariation.GurwitzD,MotulskyAG.“Drugreactions,enzymes,andbiochemic
4、algenetics”:50yearslater.Pharmacogenomics.2007;8(11):1479-84.VogelF.coinedthetermpharmacogeneticsin1959KalowW.(1962)showedthatanabnormalformofserumcholinesteraseleadstocatastrophicadversereactionstosuccinylcholine(Anectine,Quelicin),andhewrotethefirstsystematicaccountofpharmacogenetic
5、s.Audience:ThePharmacogenomicsJournalisessentialreadingforgeneticists,molecularbiologists,clinicalandmolecularpharmacologists,aswellasthoseworkinginbiotechnology,drugdiscoveryanddrugdevelopment.2001年，著名的《Nature》杂志社创立《PharmacogenomicsJournal》期刊。药物基因组学（pharmacogenomics）不仅研究机体的遗传因素对药物代谢和
6、药物反应的影响，研究基因控制药物反应的分子基础以及遗传病的药物防治途径，研究各种基因突变与药效及安全性之间的关系，根据不同人群及不同个体的遗传特征来设计和制造药物，而且还研究药物诱变、致癌、致畸等有关的遗传学问题。TheultimategoalofpharmacogenomicsA.Better,SaferDrugstheFirstTimeB.MoreAccurateMethodsofDeterminingAppropriateDrugDosagesC.AdvancedScreeningforDiseaseMalignanthyperthermia(MH)恶性高热
7、G-6-PDdeficiency----favismG-6-PD缺乏症——蚕豆病WorldwideXD（？）Xq28琥珀酰胆碱敏感症：丁酰胆碱酯酶基因BCHE的多态性FamilyBlamesSoldier'sSuicideonAnti-MalariaDrug.WashingtonPost,October12,2008CHICAGO--JuanTorresdidn'tbelievethathisson,ArmyReservistJuan"John"M.Torres,hadkilledhimselfinAfghanistanjustweeksbeforehewasto
8、retur
