title: Effect of CYP2D6*10 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer's disease.
abstract: BACKGROUND
  The aim of this study was to evaluate the effect of CYP2D6*10 and APOE polymorphisms on both steady-state plasma concentrations (Cp) and clinical response of donepezil in patients with mild-to-moderate Alzheimer's disease (AD).
  
  
  METHODS
  A total of 110 Chinese AD patients participated in this study. Patients were treated with 5 to 10 mg of donepezil daily for 6 months. The genotypes of CYP2D6*10 and APOE were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The steady-state Cp of donepezil was measured by high-performance liquid chromatography-tandem mass spectrometric assay method. The cognition of patients was evaluated at baseline and at 6-month follow-up by Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subscale.
  
  
  RESULTS
  At 6-month follow-up, 56 of 96 patients (58.3%) were evaluated as responders and 40 patients (41.7%) as nonresponders to donepezil treatment. A significantly higher frequency of patients with genotypes CYP2D6*1/*10 and *10/*10 were found in responders than in nonresponders (P < 0.05). Besides, patients with CYP2D6*1/*10 and *10/*10 genotypes had higher Cp of donepezil and improved cognition scores than those with CYP2D6*1/*1 genotype (P < 0.05). However, the frequency of APOE [Latin Small Letter Open E]4 carriers and noncarriers showed no difference between the 2 groups (P > 0.05).
  
  
  CONCLUSIONS
  AD patients with mutant allele (*10) in CYP2D6 gene may respond better to donepezil than those with wild allele (*1). We did not find the relationship between APOE [Latin Small Letter Open E]4 status and the efficacy of donepezil in our study.
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xueli
authors.initials: X
authors.lastname: Zheng
authors.forename: Ya
authors.initials: Y
authors.lastname: Miao
authors.forename: Lili
authors.initials: L
authors.lastname: Wan
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Beiyun
authors.initials: B
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D003071:Cognition / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D000077265:Donepezil; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018697:Nootropic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D001057:Apolipoproteins E; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D019389:Cytochrome P-450 CYP2D6