Effect of CYP2D6*10 and APOE Polymorphisms on the Efficacy of Donepezil in Patients With Alzheimer's Disease

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 epsilon 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 epsilon 4 status and the efficacy of donepezil in our study.