Abstract
Emerging evidence indicates that β-arrestin 2, an important regulator of G protein coupled receptors, is involved in the pathogenesis of Alzheimer’s disease (AD). The aim of this study was to investigate the association between β-arrestin 2 gene (ARRB2) variation and the risk of late-onset AD (LOAD). A total of 1132 LOAD patients and 1158 healthy controls from the Han Chinese population were included in this study. Initially, four common single nucleotide polymorphisms (SNPs) (rs3786047, rs16954146, rs1045280 and rs2271167) were selected by consulting the Han Chinese from Beijing genotype data in HapMap database. Considering the fact that these four SNPs were located in one haplotype block and any two of them were in almost complete linkage disequilibrium (D’=1, r2≥0.897), we chose rs1045280 (a coding- synonymous variant) that covered all the common genetic variations in ARRB2 with r2≥0.8 as the tag SNP (tSNP) for the subsequent genotyping. Our results showed that the minor allele of rs1045280 was associated with an increased LOAD risk after adjusting for age, gender, educational level, and the apolipoprotein E (APOE) 4 status under dominant (OR=1.291; 95% CI: 1.063-1.568; Bonferroni-corrected P=0.03) and additive (OR=1.269; 95% CI: 1.069-1.507; Bonferroni- corrected P=0.018) models. Meanwhile, when these data were stratified by APOE ε4 status, this association was evident only in APOE ε4 carriers (OR=1.617; 95% CI: 1.01-2.588; P=0.045). In summary, this study provide the first evidence that the tSNP of ARRB2 significantly increases LOAD risk in Han Chinese, suggesting ARRB2 may represent a susceptibility gene for LOAD.
Keywords: Alzheimer's disease, association, gene, polymorphism, β-arrestin 2, γ-secretase.
Current Alzheimer Research
Title:The Genetic Variation of ARRB2 is Associated with Late-onset Alzheimer's Disease in Han Chinese
Volume: 11 Issue: 4
Author(s): Teng Jiang, Jin-Tai Yu, Ying-Li Wang, Hui-Fu Wang, Wei Zhang, Nan Hu, Lin Tan, Lei Sun, Meng-Shan Tan, Xi-Chen Zhu and Lan Tan
Affiliation:
Keywords: Alzheimer's disease, association, gene, polymorphism, β-arrestin 2, γ-secretase.
Abstract: Emerging evidence indicates that β-arrestin 2, an important regulator of G protein coupled receptors, is involved in the pathogenesis of Alzheimer’s disease (AD). The aim of this study was to investigate the association between β-arrestin 2 gene (ARRB2) variation and the risk of late-onset AD (LOAD). A total of 1132 LOAD patients and 1158 healthy controls from the Han Chinese population were included in this study. Initially, four common single nucleotide polymorphisms (SNPs) (rs3786047, rs16954146, rs1045280 and rs2271167) were selected by consulting the Han Chinese from Beijing genotype data in HapMap database. Considering the fact that these four SNPs were located in one haplotype block and any two of them were in almost complete linkage disequilibrium (D’=1, r2≥0.897), we chose rs1045280 (a coding- synonymous variant) that covered all the common genetic variations in ARRB2 with r2≥0.8 as the tag SNP (tSNP) for the subsequent genotyping. Our results showed that the minor allele of rs1045280 was associated with an increased LOAD risk after adjusting for age, gender, educational level, and the apolipoprotein E (APOE) 4 status under dominant (OR=1.291; 95% CI: 1.063-1.568; Bonferroni-corrected P=0.03) and additive (OR=1.269; 95% CI: 1.069-1.507; Bonferroni- corrected P=0.018) models. Meanwhile, when these data were stratified by APOE ε4 status, this association was evident only in APOE ε4 carriers (OR=1.617; 95% CI: 1.01-2.588; P=0.045). In summary, this study provide the first evidence that the tSNP of ARRB2 significantly increases LOAD risk in Han Chinese, suggesting ARRB2 may represent a susceptibility gene for LOAD.
Export Options
About this article
Cite this article as:
Jiang Teng, Yu Jin-Tai, Wang Ying-Li, Wang Hui-Fu, Zhang Wei, Hu Nan, Tan Lin, Sun Lei, Tan Meng-Shan, Zhu Xi-Chen and Tan Lan, The Genetic Variation of ARRB2 is Associated with Late-onset Alzheimer's Disease in Han Chinese, Current Alzheimer Research 2014; 11 (4) . https://dx.doi.org/10.2174/1567205011666140317095014
DOI https://dx.doi.org/10.2174/1567205011666140317095014 |
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
-
Memantine and Kynurenic Acid: Current Neuropharmacological Aspects
Current Neuropharmacology Older and Newer Strategies for the Pharmacological Management of Agitation in Patients with Bipolar Disorder or Schizophrenia
CNS & Neurological Disorders - Drug Targets Non-Analgesic Effects of Opioids: Opioid-induced Nausea and Vomiting: Mechanisms and Strategies for their Limitation
Current Pharmaceutical Design Current Antioxidant Molecular Therapies for Oxidative Stress-Related Ailments
Current Gene Therapy A Review on the Arylpiperazine Derivatives as Potential Therapeutics for the Treatment of Various Neurological Disorders
Current Drug Targets Signal Pathways Mediating Antidepressant and Antipsychotic Drugs on Neuronal Cell Survival
Current Medicinal Chemistry - Central Nervous System Agents Simvastatin and Other HMG-CoA Reductase Inhibitors on Brain Cholesterol Levels in Alzheimers Disease
Current Alzheimer Research Synthesis of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2- a] pyrimidin-4-one Derivatives as Antibacterial Agents
Medicinal Chemistry Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants
Current Topics in Medicinal Chemistry Classical Neurotransmitters and Neuropeptides Involved in Schizophrenia: How to Choose the Appropriate Antipsychotic Drug?
Current Drug Therapy Pharmacodynamics of Memantine: An Update
Current Neuropharmacology Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives
CNS & Neurological Disorders - Drug Targets Pharmacogenetic Aspects of Neuroleptic Malignant Syndrome
Current Pharmacogenomics Inhibitors of Glycine Transporter-1: Potential Therapeutics for the Treatment of CNS Disorders
Current Topics in Medicinal Chemistry Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease
Current Medicinal Chemistry The Endocannabinoid System in Ageing: A New Target for Drug Development
Current Drug Targets Prevalence of Pre-Existing Risk Factors for Adverse Events Associated with Atypical Antipsychotics Among Commercially Insured and Medicaid Insured Patients Newly Initiating Atypical Antipsychotics
Current Drug Safety Nitric Oxide and Dietary Factors: Part IV Traditional Japanese Food (Soy Products, Fish and Tea)
Vascular Disease Prevention (Discontinued) Gene Therapy for Neurological Disorders: Challenges and Future Prospects for the Use of Growth Factors for the Treatment of Parkinsons Disease
Current Gene Therapy Proceedings of the Regional Conference of the International Society for Adolescent Psychiatry and Psychology (ISAPP), a Joint Conference with 18<sup>th</sup> National Symposium of Adolescent Mental Health, Ankara, Turkey, November 21-24, 2013<sup>1</sup>
Adolescent Psychiatry