Clinical response to cholinesterase inhibitors in dementia: the role of CYP2D6 and APOE genetic polymorphisms

Abstract The clinical response in patients with mild and moderate dementia was investigated in relation to donepezil plasmatic concentration, apolipoprotein E (APOE) and cytochrome p450 2D6 (CYP2D6) gene polymorphisms. CYP2D6 represents only 2% of all the enzymes of CYPD family and is responsible for the metabolism of most antidepressants, antipsychotics, and cholinesterase inhibitors. Some studies have investigated the association between CYP2D6 genetic variants and its phenotypes with Alzheimer disease, due to the presence of null alleles, especially the most frequent CYP2D6 ∗4. Polymorphisms in CYP2D6 gene are associated with four phenotypes related to the drug metabolized by CYP2D6: extensive metabolizers, intermediate metabolizers, poor metabolizers and ultra-rapid metabolizers. The conclusion of this study found that the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.