Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STARD Sample 英文参考文献.docVIP

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Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STARD Sample 英文参考文献.doc

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Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STARD Sample 英文参考文献

PharmacokineticGenesDoNotInfluenceResponseor TolerancetoCitalopramintheSTAR*DSample EricJ.Peters1¤,SusanL.Slager2,JeffreyB.Kraft1,GregD.Jenkins2,MeganS.Reinalda2,PatrickJ. McGrath3,StevenP.Hamilton1* 1DepartmentofPsychiatryandInstituteforHumanGenetics,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,2Departmentof Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America, 3Department of Psychiatry, Columbia University College of Physicians and SurgeonsandNewYorkStatePsychiatricInstitute,NewYork,NewYork,UnitedStatesofAmerica Abstract Background:WesoughttodeterminewhetherclinicalresponseortolerancetotheSelectiveSerotoninReuptakeInhibitor (SSRI)citalopramisassociatedwithgeneticpolymorphismsinpotentiallyrelevantpharmacokineticenzymes. Methodology: We used a two-stage case-control study design in which we split the sample of 1,953 subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial into a discovery (n=831) and validation set (n=1,046).Fifteenpolymorphismsfromfive(CYP2D6,ABCB1,CYP2C19,CYP3A4,andCYP3A5)pharmacokineticgeneswere genotyped. We examined the associations between these polymorphisms and citalopram response and tolerance. Significantassociationswerevalidatedinthesecondstageforthosepolymorphismfoundtobestatisticallysignificantin thefirststage. Conclusions: No genetic polymorphism in the pharmacokinetic genes examined was significantly associated with our response or tolerance phenotypes in both stages. For managing pharmacological treatment with citalopram, routine screeningofthecommonpharmacokineticDNAvariantsthatweexaminedappearstobeoflimitedclinicalutility. Citation:PetersEJ,SlagerSL,KraftJB,JenkinsGD,ReinaldaMS,etal.(2008)PharmacokineticGenesDoNotInfluenceResponseorTolerancetoCitalopraminthe STAR*DSample.PLoSONE3(4):e1872.doi:10.1371/journal.pone.0001872 Editor:BernhardBaune,JamesCookUniversity,Australia ReceivedOctober27,2007;AcceptedFebruary21,2008;PublishedApril