title: FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease.
abstract: OBJECTIVE
  Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer's disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD.
  
  
  METHODS
  In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion.
  
  
  RESULTS
  A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510-70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups.
  
  
  CONCLUSIONS
  FOXO1 may influence the clinical response to AChEIs in AD patients.
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gravina
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Urbano
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Leandro
authors.initials: L
authors.lastname: Cascavilla
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy ; Unit of Biostatistics, Fondazione Mario Negri Sud, Santa Maria Imbaro (CH), Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Greco
authors.affiliation: Gerontology and Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy ; Geriatrics Unit, Azienda ULSS 16 Padova, San Antonio Hospital, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics*; D001921:Brain / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005702:Galantamine / Q000627:therapeutic use; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics*; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011446:Prospective Studies; D000068836:Rivastigmine
chemical_list: D002800:Cholinesterase Inhibitors; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine
keywords: acetylcholinesterase inhibitors; forkhead box O1; response to treatment