Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations.

Détails

ID Serval
serval:BIB_88392AE9517F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations.
Périodique
Current Alzheimer Research
Auteur⸱e⸱s
Hasin Y., Avidan N., Bercovich D., Korczyn A.D., Silman I., Beckmann J.S., Sussman J.L.
ISSN
1567-2050
Statut éditorial
Publié
Date de publication
04/2005
Peer-reviewed
Oui
Volume
2
Numéro
2
Pages
207-218
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Résumé
Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. In addition, it was implicated in amyloid plaque formation, a hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment are AChE inhibitors. Thus ACHE is an obvious candidate gene for pharmacogenetic study of AD treatment. However, AChE is a highly conserved molecule, and only a few naturally occurring genetic polymorphisms have been reported in the human gene. The goals of this study were to make a systematic effort to identify natural single nucleotide polymorphisms (SNPs) in the human ACHE gene, and to reveal their population specific architecture. To this end, the genomic coding sequences for AChE of 96 unrelated control individuals from three distinct ethnic groups, African Americans, Ashkenazi Jews and Israeli Arabs, were analyzed. Thirteen ACHE SNPs were identified, ten of which are newly described, and five of which should produce amino-acid substitutions (Arg34Gln, Gly57Arg, Glu344Gly, His353Asn and Pro592Arg). Population frequencies of 11 of the 13 SNPs were established in four different populations, African Americans, Ashkenazi Jews, Sephardic Jews and Israeli Arabs; 17 haplotypes and 5 ethno-specific alleles were identified, and a cladogram of ACHE haplotypes was constructed. Among the SNPs resulting in an amino-acid substitution, three are within the mature protein, mapping on its external surface; they are thus unlikely to affect its catalytic properties, yet could have antigenic consequences or affect putative protein-protein interactions. Furthermore, the newly identified SNPs open the door to a study of the possible association of AChE with deleterious phenotypes - such as adverse drug responses to AChE inhibitors employed in treatment of AD patients and hypersensitivity to pesticides.
Mots-clé
Acetylcholinesterase/genetics, African Americans/genetics, Alleles, Amino Acid Sequence/genetics, Arabs/genetics, Chi-Square Distribution, Genetic Variation/genetics, Humans, Jews/genetics, Molecular Sequence Data, Polymorphism, Genetic/genetics, Polymorphism, Single Nucleotide/genetics, Protein Structure, Secondary/genetics, Species Specificity
Pubmed
Création de la notice
25/01/2008 16:17
Dernière modification de la notice
20/08/2019 14:47
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