Effect of CYP2D6 and CYP3A4 Genotypes on the Efficacy of Cholinesterase Inhibitors in Southern Chinese Patients With Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia, and age is strongly associated with the incidence of AD. This study aimed to investigate the association between the genotypes of CYP2D6, CYP3A4, and CYP2C9 genes to the clinical efficacy and tolerability of cholinesterase inhibitors (ChEIs) in Chinese patients with AD. One hundred seventy-nine patients with AD with newly prescribed with ChEIs were recruited. The clinical response and tolerability were evaluated at baseline, 3rd-, 6th-, and 12th-month follow-ups and were compared according to their genotypes of CYP2D6, CYP3A4, and CYP2C9. Among patients prescribed with donepezil/galantamine, CYP2D6*10 carriers showed significantly less side effects ( P = .009). CYP2D6*10 carriers responded better to ChEIs and resulted in better improvement in Alzheimer’s Disease Assessment Scale-Cognitive subscale ( P = .027) and Mini-Mental State Examination ( P = .012). Further study is required to replicate the finding, and it might be useful for clinicians to decide the medication based on the patients’ CYP genotypes.