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

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1、InterethnicDifferencesinGeneticPolymorphismsofCYP2D6intheU.S.Population:ClinicalImplicat论文InterethnicDifferencesinGeicPolymorphismsofCYP2D6intheU.S.Population:ClinicalImplicat时间:2016-07-1002:06:51阅读:次作者:freelorphism,#8226;,Hepatic,metabolism,#8226;,5-HT3-receptor,antago

2、nist,antiemetics,#8226;,.freelorphism.UnderstandthepotentialeffectsofCYP2D6polymorphismontheefficacyandsafetyfordrugsmetabolizedviathisenzyme.ListtheethnicgroupsthataremostfrequentlyaffectedbygeicvariationoftheCYP2D6enzyme.ABSTRACTDNApolymorphismshavebeenidentifiedinthe

3、genesencodinganumberofthecytochromeP450(CYP)enzymes,leadingtoetabolizesasignificantnumberofclinicallyusedmedications,andgeicvariantsoftheCYP2D6isozymethatresultinvaryinglevelsofmetabolicactivityareofclinicalimportanceinsomesettings.Theexactnatureoftheclinicaleffectcause

4、dbypolymorphismsofthegenedependsonthedruginquestionandthespecificvariantallelesexpressed,asindividualvariantsresultindifferingphenotypesaticactivity.promiseddrugefficacyduetoCYP2D6variationhasbeendocumentedberofexamples,includingthe5-HT3-receptorantagonists,iting.CYP2D6

5、isinvolvedinthemetabolismofallofthemostmonlyavailableagents,exceptgranisetron,andtheirefficacyandsideeffectsmaythereforebeaffectedbytheCYP2D6polymorphism.SignificantinterethnicdifferencesinCYP2D6allelefrequencieshavebeendemonstratedfromstudiesacrossmanycountries.Hoorphi

6、smsintheU.S.populationhavebeenchallengingtocharacterizebecauseofthecountry’sorphismmaybeemoreimportantasrobustclinicaltestsbeeultiplemedicationsandtheattendantriskfordrugdruginteractionsincreases.INTRODUCTIONItisajorityofdrugsaremetabolizedviamicrosomalenzymeslocalizedi

7、ntheliverand,toalesserextent,thesmallintestine1.TheactivityofmanydrugsdependsontheirinteractionesofthecytochromeP450(CYP)system.Theseenzymes,etabolism,displayetabolicdifferencescanalterthedoseresponserelationshipandcanhaveanumberofpossibleoutes,rangingfromtherapeuticfai

8、luretoahigherincidenceofadverseeventsandtoxicity1,2.Geicpolymorphismsindrug-metabolizingenzymesareamajorcauseo