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interethnic differences in genetic polymorphisms of cyp2d6 in the u.s. population- clinical implications

interethnic differences in genetic polymorphisms of cyp2d6 in the u.s. population- clinical implications

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页数：26页

时间：2018-10-28

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1、InterethnicDifferencesinGeneticPolymorphismsofCYP2D6intheU.S.Population:ClinicalImplications　　LEARNINGOBJECTIVES　　Afterpletingthiscourse,thereaderorphism.　　UnderstandthepotentialeffectsofCYP2D6polymorphismontheefficacyandsafetyfordrugsmetabolizedviathisenzyme.　　Listtheet

2、hnicgroupsthataremostfrequentlyaffectedbygeicvariationoftheCYP2D6enzyme.　　ABSTRACT　　DNApolymorphismshavebeenidentifiedinthegenesencodinganumberofthecytochromeP450(CYP)enzymes,leadingtoetabolizesasignificantnumberofclinicallyusedmedications,andgeicvariantsoftheCYP2D6isozy

3、methatresultinvaryinglevelsofmetabolicactivityareofclinicalimportanceinsomesettings.Theexactnatureoftheclinicaleffectcausedbypolymorphismsofthegenedependsonthedruginquestionandthespecificvariantallelesexpressed,asindividualvariantsresultindifferingphenotypesaticactivity.

4、　　promiseddrugefficacyduetoCYP2D6variationhasbeendocumentedberofexamples,includingthe5-HT3-receptorantagonists,iting.CYP2D6isinvolvedinthemetabolismofallofthemostmonlyavailableagents,exceptgranisetron,andtheirefficacyandsideeffectsmaythereforebeaffectedbytheCYP2D6polymor

5、phism.　　SignificantinterethnicdifferencesinCYP2D6allelefrequencieshavebeendemonstratedfromstudiesacrossmanycountries.HoorphismsintheU.S.populationhavebeenchallengingtocharacterizebecauseofthecountry’sorphismmaybeemoreimportantasrobustclinicaltestsbeeultiplemedicationsand

6、theattendantriskfordrugdruginteractionsincreases.　　INTRODUCTION　　Itisajorityofdrugsaremetabolizedviamicrosomalenzymeslocalizedintheliverand,toalesserextent,thesmallintestine[1].TheactivityofmanydrugsdependsontheirinteractionesofthecytochromeP450(CYP)system.Theseenzymes,e

7、tabolism,displayetabolicdifferencescanalterthedoseresponserelationshipandcanhaveanumberofpossibleoutes,rangingfromtherapeuticfailuretoahigherincidenceofadverseeventsandtoxicity[1,2].Geicpolymorphismsindrug-metabolizingenzymesareamajorcauseofvariabilityindrugmetabolismtha

8、tleadstotheoccurrenceofadverseeffectsorlackoftherapeuticefficacy[1].　　Morethan50humanCYPisozymeshavebee

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