The roles of apolipoprotein E3 and CYP2D6 (rs1065852) gene polymorphisms in the predictability of responses to individualized therapy with donepezil in Han Chinese patients with Alzheimer's disease

Abstract

Aim: Polymorphisms in the apolipoprotein E and CYP2D6 genes are widely reported to be related to Alzheimer's disease. However, few studies have focused on the relationship between polymorphisms in apolipoprotein E and CYP2D6 (rs1065852) genes and therapeutic responses to donepezil (DNP). This study explored the influence of apolipoprotein E3 and CYP2D6 (rs1065852) gene polymorphisms on therapeutic responses to donepezil in Han Chinese patients with Alzheimer's disease.

Materials and methods: A total of 85 patients with mild to moderate Alzheimer's disease who were treated with 2.5-10mg of DNP per day for at least 3 months were enrolled. Mini-Mental State Examination scores were measured before and after DNP treatment, and the apolipoprotein E3 and CYP2D6 (rs1065852) genotypes of the patients were determined.

Results: We found that ApoE E3 non-carriers responded better to DNP treatment than E3 carriers (p=0.000) and that CYP2D6*10/*10 patients (MMSE score change: 0.29±3.27) exhibited better therapeutic responses to DNP than did CYP2D6*1/*1 and CYP2D6*1/*10 patients (p=0.033). Patients who were ApoE E3 non-carriers and who had the CYP2D6*10/*10 genotype exhibited a trend toward better clinical responses to DNP therapy.

Conclusions: The ApoE E3 allele and the CYP2D6 rs1065852 polymorphism may provide clinically relevant information for predicting therapeutic responses to DNP therapy.

Keywords: Apolipoprotein E3; CYP2D6 rs1065852 polymorphism; Donepezil; Han Chinese patients; Individualized therapy.