title: A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a devastating neurodegeneration with a characteristic deficit in cholinergic neurotransmission. Treatment with acetylcholinesterase (AChE) inhibitors aims to reverse this deficit and does ameliorate the decline in cognition in some AD patients, although response is variable.
  
  
  OBJECTIVE
  To examine whether sequence variation in the gene encoding choline acetyltransferase (CHAT), which encodes the major catalytic enzyme of the cholinergic pathway, predicts response to AChE inhibitors.
  
  
  METHODS
  Alzheimer's disease patients (121) were treated with cholinesterase inhibitors and the effect of treatment on cognition was measured using the Mini Mental State Examination (MMSE). Six polymorphisms in CHAT were analysed for association with change in MMSE score.
  
  
  RESULTS
  After correction for multiple testing, we found one SNP, rs733722, in a promoter region of CHAT, is associated with response of AD patients to cholinesterase inhibitors (P = 0.03) and accounts for 6% of the variance in response to AChE inhibitors.
  
  
  CONCLUSIONS
  Rs733722 represents a putative marker of response to AChE inhibitors in AD patients.
authors.affiliation: Department of Psychological Medicine, Cardiff University, Cardiff, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Harold
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Cathryn E
authors.initials: CE
authors.lastname: Patterson
authors.forename: Paul
authors.initials: P
authors.lastname: Hollingworth
authors.forename: Pamela
authors.initials: P
authors.lastname: Moore
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
authors.forename: Peter
authors.initials: P
authors.lastname: Passmore
authors.forename: Stephen
authors.initials: S
authors.lastname: McIlroy
authors.forename: Lesley
authors.initials: L
authors.lastname: Jones
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics*; D002384:Catalysis; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D002800:Cholinesterase Inhibitors; D002795:Choline O-Acetyltransferase