title: Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer's Disease.
abstract: BACKGROUND
  Cholinergic transmission loss is one of the major features in Alzheimer&amp;#039;s Disease (AD). Acetylcholinesterase inhibitors (AChEI) are moderately active in AD. α7nAChR (alpha-7 nicotinic acetylcholine receptor), encoded by CHRNA7 (Nicotinic Cholinergic Receptor Alpha-7 gene), is involved in the cholinergic neurotransmission and AD pathogenesis. α7nAChR is a putative receptor of amyloid beta (Aβ). The complex α7nAChR-Aβ is found in neuritic plaques and AD cortical neurons. In normal physiologic conditions, α7nAChR-Aβ interaction leads to receptor activation. Genetic polymorphisms (SNPs) of CHRNA7 and/or CHRFAM7A (fusion gene containing CHRNA7 partial duplication) may be a possible susceptibility trait to dementia, potentially useful to identify high risk or responder individuals. CHRFAM7A-2-bp deletion or CHRNA7 SNPs (rs1514246, rs2337506, rs8027814) seem protective factors in different forms of dementia including AD.
  
  
  OBJECTIVE
  Correlation between(SNPs) of CHRNA7 and/or CHRFAM7A and cholinesterase inhibitors in AD.
  
  
  METHODS
  Literature review.
  
  
  RESULTS
  Among the leading AD therapeutics, Donepezil (DP) and galantamine (AChEI) induce upregulation of α7nAChR protein levels, protecting neurons from degeneration. Patients carrying rs8024987 (C/G) or rs6494223 (C/T) respond better to AChEI. In the caucasic population rs6494223 TT subjects are 7-15% of the total. α7nAChR upregulation induced by DP is higher in lymphocytes from TT subjects than in CC or CT as well as calcium uptake.
  
  
  CONCLUSIONS
  The correlation between genetic and functionality data may have an impact on several aspects of disease presentation and therapy, helping in prediction pattern of AD presentation and treatment efficacy. As a consequence it may lead to better patients quality of life and longer periods of self- sufficiency. Moreover, it may contribute to clarify AChEI mechanisms of action.
authors.affiliation: Laboratory of Molecular Epidemiology, IRCCS "San Raffaele Pisana" Via di Valcannuta, 247 I- 00166 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Russo
authors.affiliation: Clinical and Molecular Epidemiology Division, IRCCS "San Raffaele Pisana" Via di Valcannuta, 247, I-00166 Rome, Italy.
authors.forename: Aliaksei
authors.initials: A
authors.lastname: Kisialiou
authors.affiliation: Clinical and Molecular Epidemiology Division, IRCCS "San Raffaele Pisana" Via di Valcannuta, 247, I-00166 Rome, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Moroni
authors.affiliation: Clinical and Molecular Epidemiology Division, IRCCS "San Raffaele Pisana" Via di Valcannuta, 247, I-00166 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Prinzi
authors.affiliation: Scientific Direction, IRCCS "San Raffaele Pisana" Via di Valcannuta, 247, I-00166 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D005702:Galantamine / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000071184:Pharmacogenomic Variants; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D015854:Up-Regulation; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D007189:Indans; D010880:Piperidines; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine; D000077265:Donepezil
keywords: AChEI-cognitive response; AD pathogenesis; Acetylcholinesterase inhibitors (AChEI); CHRNA7; cholinergic transmission; donepezil; galantamine; genetic polymorphisms (SNPs)