Effect of a
            <i>CYP2D6</i>
            polymorphism on the efficacy of donepezil in patients with Alzheimer disease

Pilotto, Alberto; Franceschi, M.; D’Onofrio, Grazia; Bizzarro, Alessandra; Mangialasche, Francesca; Cascavilla, Leandro; Paris, Francesco; Matera, Maria G.; Pilotto, Andrea; Daniele, Antonio; Mecocci, Patrizia; Masullo, Carlo; Dallapiccola, Bruno; Seripa, Davide

doi:10.1212/wnl.0b013e3181b6bbe3

Cited by 101 publications

(70 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients were treated for 3 months, and response to the treatment was deﬁned conservatively according to the NICE criteria as patients who show improvement or no deterioration in cognition and improvement in functional status (The National Health Service Constitution). The genotypes were correlated with the drug levels according to MMSE classiﬁcation and according to the genotypes (0, 1, or 2 mutant alleles) [4,28]. In this study, a large interindividual variability in the C/D ratio of donepezil monotherapy was observed, and this variability was signiﬁcantly correlated with the CYP3A4 genotypes for patients on donepezil monotherapy.…”

Section: Discussionmentioning

confidence: 69%

“…Donepezil is metabolized mainly by the cytochrome p450 enzymes CYP2D6 and 3A [2]. However, some studies have reported an impact of CYP polymorphisms on the drug levels in patients on donepezil monotherapy [3,4,5]. So far, no studies have found a correlation between relevant CYP2D6 and CYP3A4 genotypes in patients undergoing donepezil combination therapy and drug levels and clinical response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of CYP2D6 and CYP3A4 Genetic Polymorphism on Combined Cholinesterase Inhibitors and Memantine Treatment in Mild to Moderate Alzheimer's Disease

Nirmal

Tripathi²,

Sagar³

et al. 2013

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Aim: The impact of CYP2D6 and CYP3A4 polymorphism on the steady-state plasma concentrations and therapeutic outcome of donepezil monotherapy and combination therapy in Alzheimer's disease (AD) patients. Methods: A total of 38 patients for donepezil and 17 patients for donepezil and memantine therapy, aged ≥55 years, were recruited meeting inclusion and exclusion criteria. Polymerase chain reaction-restriction fragment length polymorphism was performed. The liquid chromatography-tandem mass spectrometry method was used for estimation of drug levels of donepezil and memantine. Results: Significant allele frequency was observed for CYP2D6*3 polymorphism in patients on donepezil monotherapy and combination therapy. Significant allele frequency for CYP2D6*4 was observed in the patients on donepezil monotherapy. Conclusion: CYP2D6 polymorphism, though not significant, might partially be involved in the plasma concentration of AD drug.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Impact of CYP2D6 and CYP3A4 Genetic Polymorphism on Combined Cholinesterase Inhibitors and Memantine Treatment in Mild to Moderate Alzheimer's Disease

Nirmal

Tripathi²,

Sagar³

et al. 2013

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…Even though the same scales were applied to assess responsiveness to treatment in particular studies, the definitions for treatment response were different. Some studies defined responders as those who obtained the same or higher MMSE scores after a defined period of treatment [16,17]. Raschetti et al [18] defined response to treatment as an increase of at least 2 points in the MMSE after 9 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 1 Gene Polymorphisms Do Not Influence the Response to Treatment in Alzheimer’s Disease

Klimkowicz-Mrowiec

Marona²,

Spisak

et al. 2011

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background: Acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with Alzheimer’s disease (AD). However, their efficacy is moderate and differs from patient to patient. Recent studies suggest that the Q192R variant of the paraoxonase 1 gene (PON1) might affect individual susceptibility to these drugs. Methods: We investigated the influence of 3 single nucleotide polymorphisms (SNPs) in PON1 (rs 662, rs 854560, rs 705381) and the APOE common polymorphism in 101 Polish patients with late-onset AD in response to treatment with AChEIs. Results: No significant differences were observed between carriers and non-carriers of the PON1 SNPs or the APOE common polymorphism in terms of treatment response. These results did not change after stratification of APOE status. Conclusion: Our results suggest that both the investigated PON1 and APOE common SNPs do not influence treatment response to AChEIs in patients with AD.

show abstract

“…CYP2D6 was closely associated with the dopamine transporter and rat brain-specific CYP2D18 has been implicated in dopamine metabolism (119). Pilotto et al (120) demonstrated that, in patients with mild to moderate AD, SNP rs1080985 in CYP2D6 may influence the clinical efficacy of donepezil. Whereas, Liu et al (121) found no significant association between rs1080985 SNP in CYP2D6 and common APOE polymorphisms in a Chinese population.…”

Section: Cytochrome P450 Family 2 Subfamily D Member 6 (Cyp2d6)mentioning

confidence: 99%

Unraveling the genes implicated in Alzheimer's disease

Giri¹,

Shah²,

Upreti³

et al. 2017

Biomedical Reports

View full text Add to dashboard Cite

Abstract. Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder and it is the most common form of dementia in the elderly. Early onset AD is caused by mutations in three genes: Amyloid-β precursor protein, presenilin 1 (PSEN1) and PSEN2. Late onset AD (LOAD) is complex and apolipoprotein E is the only unanimously accepted genetic risk factor for its development. Various genes implicated in AD have been identified using advanced genetic technologies, however, there are many additional genes that remain unidentified. The present review highlights the genetics of early and LOAD and summarizes the genes involved in different signaling pathways. This may provide insight into neurodegenerative disease research and will facilitate the development of effective strategies to combat AD.

show abstract

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

Cited by 101 publications

References 35 publications

Impact of CYP2D6 and CYP3A4 Genetic Polymorphism on Combined Cholinesterase Inhibitors and Memantine Treatment in Mild to Moderate Alzheimer's Disease

Impact of CYP2D6 and CYP3A4 Genetic Polymorphism on Combined Cholinesterase Inhibitors and Memantine Treatment in Mild to Moderate Alzheimer's Disease

Paraoxonase 1 Gene Polymorphisms Do Not Influence the Response to Treatment in Alzheimer’s Disease

Unraveling the genes implicated in Alzheimer's disease

Contact Info

Product

Resources

About