Abstract
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 Alzheimers 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 aminoacid 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.
Keywords: acetylcholinesterase, ache, single nucleotide polymorphism, snp, alzheimers disease, adverse drug reaction
Current Alzheimer Research
Title: Analysis of Genetic Polymorphisms in Acetylcholinesterase as Reflected in Different Populations
Volume: 2 Issue: 2
Author(s): Yehudit Hasin, Nili Avidan, Dani Bercovich, Amos D. Korczyn, Israel Silman, Jacques S. Beckmann and Joel L. Sussman
Affiliation:
Keywords: acetylcholinesterase, ache, single nucleotide polymorphism, snp, alzheimers disease, adverse drug reaction
Abstract: 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 Alzheimers 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 aminoacid 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.
Export Options
About this article
Cite this article as:
Hasin Yehudit, Avidan Nili, Bercovich Dani, Korczyn D. Amos, Silman Israel, Beckmann S. Jacques and Sussman L. Joel, Analysis of Genetic Polymorphisms in Acetylcholinesterase as Reflected in Different Populations, Current Alzheimer Research 2005; 2 (2) . https://dx.doi.org/10.2174/1567205053585909
DOI https://dx.doi.org/10.2174/1567205053585909 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets
Current Pharmaceutical Biotechnology Microglia and Inflammation in Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Mechanisms and Treatment of Neuropathic Pain
Central Nervous System Agents in Medicinal Chemistry Endostatin: Preclinical Development as an Anticancer Agent
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Heme Oxygenase-1 in Vascular Smooth Muscle Cells Counteracts Cardiovascular Damage Induced by Angiotensin II
Current Neurovascular Research Ideational Fluency in Patients with Rheumatoid Arthritis
Current Rheumatology Reviews Non-Invasive Imaging of Ferucarbotran Labeled INS-1E Cells and Rodent Islets in Vitro and in Transplanted Diabetic Rats
Current Pharmaceutical Biotechnology Intracellular Ca<sup>2+</sup> Signals to Reconstruct A Broken Heart: Still A Theoretical Approach?
Current Drug Targets Editorial [Hot Topic: Recent Developments in Adaptive and Innate Mechanisms of Mucosal Immunity (Executive Editor: Pearay L. Ogra)]
Current Molecular Medicine The Interaction of Dietary Fibres with the Colon
Current Nutrition & Food Science Adrenomedullin in Hypertension
Current Hypertension Reviews Molecular Modeling Based Synthesis and Evaluation of <i>In vitro</i> Anticancer Activity of Indolyl Chalcones
Current Topics in Medicinal Chemistry Chemokines in Cardiovascular Remodeling: Clinical and Therapeutic Implications
Current Molecular Medicine The Renin-Angiotensin System: New Insight into Old Therapies
Current Medicinal Chemistry COVID-19 and Tuberculosis: Two Knives in a Sheath
Coronaviruses Possible Roles of Microglial Cells for Neurotoxicity in Clinical Neurodegenerative Diseases and Experimental Animal Models
Inflammation & Allergy - Drug Targets (Discontinued) Oxidative Stress, HDL and Atherosclerosis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Link between Metabolic Syndrome and Insulin Resistance
Current Vascular Pharmacology Albumin Competitively Inhibits Glycation of Less Abundant Proteins
Protein & Peptide Letters Patents in Targets and Drugs for Unbalanced Cytokine and Chemokine Network Mediated Disorders
Recent Patents on Inflammation & Allergy Drug Discovery