title: CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease.
abstract: BACKGROUND
  CHRNA7 encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response.
  
  
  METHODS
  Mild to moderate AD patients received ChEIs were recruited from the neurology clinics of three teaching hospitals from 2007 to 2010 (n = 204). Nine haplotype-tagging single nucleotide polymorphisms of CHRNA7 were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ≥ 2 between baseline and 6 months after ChEI treatment.
  
  
  RESULTS
  AD women carrying rs8024987 variants [GG+GC vs. CC: adjusted odds ratio (AOR) = 3.62, 95% confidence interval (CI) = 1.47-8.89] and GG haplotype in block1 (AOR = 3.34, 95% CI = 1.38-8.06) had significantly better response to ChEIs (false discovery rate <0.05). These variant carriers using galantamine were 11 times more likely to be responders than female non-carriers using donepezil or rivastigmine.
  
  
  CONCLUSIONS
  For the first time, this study found a significant association between CHRNA7 polymorphisms and better ChEI response. If confirmed by further studies, CHRNA7 polymorphisms may aid in predicting ChEI response and refining treatment choice.
authors.affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan ; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Weng
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ; Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jen-Hau
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.affiliation: Department of Neurology, En Chu Kong Hospital, Taipei, Taiwan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine, En Chu Kong Hospital, Taipei, Taiwan.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wen
authors.affiliation: Center of Neurological Medicine, Cardinal Tien Hospital, Taipei, Taiwan ; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
authors.affiliation: Department of Laboratory Medicine, Cardinal Tien Hospital, Taipei, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chu
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan ; Research Center for Genes, Environment and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor