BCHE and CYP2D6 genetic variation in Alzheimer's disease patients treated with cholinesterase inhibitors

摘要: Purpose Cholinesterase inhibitors are commonly prescribed to patients with Alzheimer’s disease (AD) enhance cholinergic neurotransmission. Differential response these treatmentshasbeenobserved,andclaimshavebeenmadethat individualgeneticvariantsmayinfluencethepharmacokinetic and pharmacodynamic properties of drugs. Here we assess the effects genetic variation at two loci involved in activity cholinesterase on longitudinal clinical change AD being treated donepezil, galantamine, rivastigmine. Methods This was an open study which 171 Italian donepezil (n=92), galantamine (n=33), or rivastigmine (n=46) were enrolled. Response treatment quantified by grading patient’s cognitive state (MiniMental State Examination) ability perform normal daily activities (Activities Daily Living, Instrumental Activities Living) baseline after 6 12 months treatment. Genetic comprehensively characterized analyzed loci: CYP2D6, is metabolism, BCHE, codes for enzyme (butyrylcholinesterase) both target metabolizer APOE (coding apolipoprotein E), associated risk inefficacy specific treatments, genotyped control patient stratification. The influence CYP2D6 BCHE genotype changes evaluated several tests association. Results After 1 year treatment, 29, 12, receiving rivastigmine, respectively, showed a decrement, while eight patientsinterruptedthetherapybefore12monthsoftreatment. No significant differences between three treatments observed terms tolerability. Nonresponders show higher proportion mutated alleles, but not reliable predictor inhibitors. Conclusions Individualized therapy based genotypes unlikely be beneficial treating routine practice.