Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease.

Abstract:

OBJECTIVE:To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 (CYP2D6) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). METHODS:This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5-10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion. RESULTS:At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490-7.901). CONCLUSIONS:The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.

journal_name

Neurology

journal_title

Neurology

authors

Pilotto A,Franceschi M,D'Onofrio G,Bizzarro A,Mangialasche F,Cascavilla L,Paris F,Matera MG,Pilotto A,Daniele A,Mecocci P,Masullo C,Dallapiccola B,Seripa D

doi

10.1212/WNL.0b013e3181b6bbe3

subject

Has Abstract

pub_date

2009-09-08 00:00:00

pages

761-7

issue

10

eissn

0028-3878

issn

1526-632X

pii

73/10/761

journal_volume

73

pub_type

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