Pharmacogenetic Study on the Effect of Rivastigmine on PS2 and APOE Genes in Iranian Alzheimer Patients.

BACKGROUND/AIMS: Alzheimer disease (AD) is a complex and genetically heterogeneous disorder, and certain genes such as PS2 and APOE4 contribute to the development of AD. Due to its heterogeneity, AD-predisposing genes could vary in different populations. Moreover, not all AD patients will respond to the same therapy. We specifically investigated the effect ofrivastigmine (Exelon) on PS2 and APOE genes in Iranian AD patients.

METHODS: A total of 100 AD patients, 67 patients with sporadic AD (SAD) and 33 patients with familial AD (FAD), receiving rivastigmine therapy and 100 healthy controls were studied. PCR-RFLP was used for genotyping of PS2 and APOE.

RESULTS: We found a positive association between the PS2 -A allele and SAD patients (p(c) = 0.01), and the PS2 +A/-A genotype was significantly more frequent in SAD than FAD patients (p(c) = 0.009). The APOE4 allele was associated with total AD, SAD and FAD (p(c) = 0.000002). Patients with the PS2 +A/-A genotype and bigenic genotypes of +A/-A·∊3/∊3 and +A/-A·∊3/∊4 were the best responders to Exelon therapy, and those with the PS2 +A/+A and APOE ∊3/∊4 genotypes were the worst responders.

CONCLUSION: Our findings suggest that the PS2 and APOE4 alleles and genotypes affect both AD risk and response to rivastigmine therapy.