• J Formos Med Assoc · Jan 2022

    Impact of the CYP2D6 single nucleotide polymorphism on the concentration of and therapeutic response to donepezil in mild-to-moderate Alzheimer's disease.

    • Ping-Song Chou, Ling-Chun Huang, Tzyh-Chyuan Hour, Chen-Wen Yen, and Yuan-Han Yang.
    • Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of and Master's Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
    • J Formos Med Assoc. 2022 Jan 1; 121 (1 Pt 2): 409-415.

    Background/PurposeDonepezil was approved for the treatment of Alzheimer's disease (AD) but causes variable therapeutic responses. Thus, identifying specific genetic polymorphisms, which can predict a therapeutic response to donepezil, would enable a development of personalized strategy to treatment for patients with AD. The research aimed to exam the impact of the cytochrome P450 2D6 (CYP2D6) single nucleotide polymorphism (SNP) rs1080985 on the concentration of and therapeutic response to donepezil in AD.MethodsIn total, 40 newly diagnosed AD patients who had a clinical dementia rating (CDR) of 0.5-2 and who were on donepezil were enrolled and followed up. Plasma concentrations of donepezil were determined after 6 months of donepezil treatment. Cognitive and functional statuses were evaluated annually during follow-up. The response to therapy was defined based on the change in CDR.ResultsAt a mean of 21.8 ± 5.7 months of follow-up, 10 of 40 patients (25.0%) were nonresponders to donepezil treatment. Patients who were homozygous for the G allele exhibited a higher concentration of donepezil and concentration-to-dose ratio than those with other genotypes. Furthermore, a significantly higher proportion of patients with the G/G genotype were responders than nonresponders (90.0% vs 50.0%, P = 0.015, effect size of V: 0.457) to donepezil treatment. Conversely, patients carrying the C allele had a significantly high risk of poor responses to donepezil treatment (odds ratio: 9.00, 95% confidence interval: 1.611-50.275).ConclusionThe CYP2D6 SNP rs1080985 might be a useful pharmacogenetic marker of the long-term therapeutic response to donepezil in patients with AD.Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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