Influence of rs1080985 single nucleotide polymorphism of the CYP2D6 gene on response to treatment with donepezil in patients with Alzheimer’s disease

Abstract

Aleksandra Klimkowicz-Mrowiec,1 Pawel Wolkow,2 Malgorzata Sado,3 Anna Dziubek,3 Joanna Pera,1 Tomasz Dziedzic,1 Andrzej Szczudlik,1 Agnieszka Slowik1 1Department of Neurology, Jagiellonian University, School of Medicine, Botaniczna, 2Department of Pharmacology, Jagiellonian University, School of Medicine, Grzegórzecka, 3Department of Neurology, University Hospital, Botaniczna, Krakow, Poland Background: Recent data indicate that the rs1080985 single nucleotide polymorphism of the cytochrome P450 (CYP) 2D6 gene may affect the response to treatment with donepezil in patients with Alzheimer's disease. There is also evidence that the common apolipoprotein E (APOE) polymorphism may affect the response to treatment with donepezil in Alzheimer's disease. We investigated the association between response to donepezil and the rs1080985 single nucleotide polymorphism, the minor allele (G) of which was previously reported to be associated with a poor response to this drug in patients with Alzheimer's disease. The common APOE polymorphism was also assessed for its relevance to the outcome of this treatment. Methods: Analysis of CYP2D6 and APOE polymorphisms was undertaken in 88 naive Caucasian patients with Alzheimer's disease. All patients received treatment with donepezil for at least 10 months, and the response to treatment was then assessed according to the National Institute for Health and Clinical Excellence criteria. Results: No significant differences were observed in distribution of the CYP2D6 rs1080985 single nucleotide polymorphism or common APOE polymorphism between responders (68.2%) and nonresponders (31.8%) to treatment with donepezil. Conclusion: Our results suggest that neither the CYP2D6 nor the APOE polymorphism influences the response to treatment with donepezil in a Polish population with Alzheimer’s disease. Keywords: Alzheimer’s disease, CYP2D6, APOE, donepezil, pharmacogenetics, single nucleotide polymorphism