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Effect of CYP2D6*10 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer’s disease


Zhong, Yuan, Zheng, Xueli, Miao, Ya, Wan, Lili, Yan, Hong, Wang, Beiyun


The American Journal Of The Medical Sciences, Volume: 345, No.: 3, Pages.: 222-226

Year of Publication



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.;

Bibtex Citation

@article{Zhong_2013, doi = {10.1097/maj.0b013e318255a8f9}, url = {}, year = 2013, month = {mar}, publisher = {Elsevier {BV}}, volume = {345}, number = {3}, pages = {222--226}, author = {Yuan Zhong and Xueli Zheng and Ya Miao and Hong Yan and Beiyun Wang and Lili Wan}, title = {Effect of {CYP}2D6{ast}10 and {APOE} Polymorphisms on the Efficacy of Donepezil in Patients With Alzheimer's Disease}, journal = {The American Journal of the Medical Sciences} }


administration & dosage, aged, aged, 80 and over, alleles, alzheimer disease, apolipoproteins e, blood, cognition, donepezil, drug effects, drug therapy, female, gene frequency, geneotypes, genetics, humans, indans, linked, male, metabolism, middle aged, mutation, nootropic agents, pharmacokinetics, piperidines, polymorphism restriction fragment length, response, to

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Before and After Study

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime