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Variability of AChE, BChE, and ChAT genes in the late‐onset form of Alzheimer's disease and relationships with response to treatment with Donepezil and Rivastigmine
Author(s) -
Scacchi Renato,
Gambina Giuseppe,
Moretto Giuseppe,
Corbo Rosa Maria
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30846
Subject(s) - butyrylcholinesterase , acetylcholinesterase , rivastigmine , choline acetyltransferase , single nucleotide polymorphism , donepezil , genotype , odds ratio , cholinesterase , medicine , allele , oncology , cholinergic , disease , case control study , psychology , dementia , aché , genetics , biology , gene , enzyme , biochemistry
Several factors are believed to give rise to the late onset sporadic form of Alzheimer's disease (LOAD). We have studied the variation at the genes of three enzymes of the cholinergic system: acetylcholinesterase, butyrylcholinesterase, and choline acetyltransferase. The single nucleotide polymorphisms (SNPs) examined were: AChE rs2571598, BChE rs1355534, BChE rs1803274, and ChAT rs2177369. The sample for the case–control study was 471 LOAD patients aged 60 years or older, and 254 subjects with no neurodegenerative disorders as the control group. A significant difference in the genotype distribution between patients and controls was observed only for ChAT rs2177369, showing that the G/G genotype was to be considered a risk factor with respect to the G/A + A/A genotypes (odds ratio = 1.56; 95% Confidence Interval = 1.10–2.22; P = 0.01). Though indicating a significant association with AD onset, our results are far from definitive since contrast with the ones reported by other authors in a previous case–control study, and call for further investigations. Among patients, 171 took part in an observational study concerning the possible role of the genetic composition on the efficacy of treatment with Donepezil and Rivastigmine. We related the SNPs of the above cited genes with cognitive status measured by MMSE. Carrying an allele or a genotype of these SNPs does not seem to play a relevant role in the response to treatment with the two cholinesterase inhibitors, though some significant results were found associated with the AChE A/A genotype that had the best response when treated with Rivastigmine. © 2008 Wiley‐Liss, Inc.