Involvement of APOE polymorphism in Alzheimer's disease susceptibility and Donepezil response in Moroccan patients

Background: Donepezil (DNP) is an acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease (AD). Apolipoprotein E (ApoE) is reported to be a strong genetic risk factor for AD. The aim of this study was to evaluate the impact of ApoE gene polymorphism on susceptibility to AD and response to Donepezil in Moroccan patients. Methods: A total of 70 Moroccan AD patients and 63 healthy controls participated to this study. Patients were treated with 5 to 10 mg of DNP daily for 6 months and 12 months later. The genotype analysis of ApoE gene was performed by PCR-RFLP method. Results: A statistically significant difference was observed in allelic and genotypic frequencies of ApoE gene polymorphism among cases and controls. The epsilon 2 allele was significantly associated with increased risk of AD (OR [95% CI] = 3.3 [1.8-6.08], p = 0.0001). Furthermore, the epsilon 2/epsilon 2 and epsilon 2/epsilon 4 genotypes were more frequent in AD patients than controls (OR [95% CI] = 17.64 [3.68-84.9], p = 0.0003; OR [95% CI] = 3.53 [1.03-12.04], p = 0.044, respectively). However, no association was observed between ApoE epsilon 4 status and clinical features, as well as between ApoE gene polymorphism and response to DNP treatment. In addition, a higher rate of the epsilon 2/epsilon 2 genotype was observed in patients with severe stage of AD. Conclusions: Our study suggests that epsilon 2 allele of the ApoE gene may represent a genetic risk factor for AD in Moroccan patients. On the other hand, ApoE genotypes seem to have no effect on response to DNP. However, more larger studies must be conducted in order to confirm the present findings.