Replication Study to Confirm the Role of CYP2D6 Polymorphism rs1080985 on Donepezil Efficacy in Alzheimer's Disease Patients

Article type: Short Communication

Authors: Albani, Diego^{a; *; 1} | Boneschi, Filippo Martinelli^{b; 1} | Biella, Gloria^a | Giacalone, Giacomo^b | Lupoli, Sara^b | Clerici, Francesca^c | Benussi, Luisa^d | Ghidoni, Roberta^e | Galimberti, Daniela^f | Squitti, Rosanna^{g; h} | Mariani, Stefania^h | Confaloni, Annamariaⁱ | Bruno, Giuseppe^j | Mariani, Claudio^c | Scarpini, Elio^f | Binetti, Giuliano^d | Magnani, Giuseppe^k | Franceschi, Massimo^l | Forloni, Gianluigi^a

Affiliations: [a] Department of Neuroscience, “Mario Negri” Institute for Pharmacological Research, Milan, Italy | [b] INSPE, San Raffaele Scientific Institute, Milan, Italy | [c] Centre for Research and Treatment on Cognitive Dysfunction, Neurology Unit, Luigi Sacco Hospital, University of Milan, Milan, Italy | [d] NeuroBioGen Lab-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [e] Proteomics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [f] Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, “Fondazione Cà Granda, IRCCS Ospedale Policlinico”, Milan, Italy | [g] Department of Neuroscience, AFaR – Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy | [h] Department of Neurology, “Campus Biomedico” University, Rome, Italy | [i] Istituto Superiore di Sanità, Department of Cell Biology and Neurosciences, Rome, Italy | [j] Department of Neurology and Psychiatry, University of Rome “Sapienza”, Rome, Italy | [k] Department of Neurology, Clinical Neurophysiology and Neurorehabilitation, San Raffaele Scientific Institute, Milan, Italy | [l] Department of Neurology, IRCCS Multimedica, Milan, Italy

Correspondence: [*] Correspondence to: Dr. Diego Albani, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156 Milan, Italy. Tel.: +39 02 39014594; Fax: +39 02 3546277, E-mail: diego.albani@marionegri.it.

Note: [1] These authors contributed equally to the work.

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder often treated with donepezil, an acetylcholinesterase inhibitor. Response to donepezil is variable, probably based on patients' genetic background in donepezil metabolizing enzymes, including cytochrome 2D6 (CYP2D6). We evaluated the association between clinical response to donepezil and a common variant (rs1080985) of CYP2D6, previously reported to be associated with poor response to the drug. In a sample of 415 AD cases, we found evidence of association between rs1080985 and response to donepezil after 6 months of therapy (OR [95% CI]: 1.74 [1.01–3.00], p = 0.04). Rs1080985 might be useful as predictor of poor response to short-term donepezil treatment.

Keywords: Alzheimer's disease, apolipoprotein E, CYP2D6, donepezil, pharmacogenetics, rs1080985

DOI: 10.3233/JAD-2012-112123

Journal: Journal of Alzheimer's Disease, vol. 30, no. 4, pp. 745-749, 2012