Abstract
Toll-like receptor 4 (TLR4) represents a reasonable functional and positional candidate gene for Alzheimer’s disease (AD) as it is located within the previous identified linkage region of AD on chromosome 9q, and functionally is involved in the microglia-mediated inflammatory response, amyloid-β (Aβ) plaque formation and Aβ clearance. To test whether variants in the TLR4 gene are associated with late-onset AD (LOAD), we organized a multicenter study of 785 subjects (399 cases and 386 matched controls) in a Han Chinese population. Ten single nucleotide polymorphisms (SNPs) that span the TLR4 gene, from approximately 5 kb of the predicted 5’-untranslated region (UTR) to approximately 6 kb of the predicted 3’- UTR, were selected and their associations with LOAD risk factors were assessed. With respect to allelic diversity, the minor alleles of seven SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs7037117, and rs7045953) in TLR4 showed consistent protective effects against the risk of developing LOAD. With regard to genotypic diversity, individuals carrying at least one minor allele of each SNP above had a consistently lower risk of LOAD than those with no copies of the minor alleles (ORs ranging from 0.445 to 0.637). rs7045953, located in the 3’-UTR of TLR4, was most strongly associated with LOAD, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 1.7x10-6, Pc s1.0x10-4). Our data suggests that the TLR4 gene contributes to the susceptibility for LOAD in Han Chinese.
Keywords: Alzheimer’s disease, toll-like receptor 4, polymorphism, candidate gene, susceptibility, amyloid-ß (Aß) plaques, cytokines
Current Alzheimer Research
Title:Common Variants in Toll-Like Receptor 4 Confer Susceptibility to Alzheimer’s Disease in a Han Chinese Population
Volume: 9 Issue: 4
Author(s): Jin-Tai Yu, Dan Miao, Wei-Zhen Cui, Jiang-Rong Ou, Yan Tian, Zhong-Chen Wu, Wei Zhang, Lan Tan
Affiliation:
Keywords: Alzheimer’s disease, toll-like receptor 4, polymorphism, candidate gene, susceptibility, amyloid-ß (Aß) plaques, cytokines
Abstract: Toll-like receptor 4 (TLR4) represents a reasonable functional and positional candidate gene for Alzheimer’s disease (AD) as it is located within the previous identified linkage region of AD on chromosome 9q, and functionally is involved in the microglia-mediated inflammatory response, amyloid-β (Aβ) plaque formation and Aβ clearance. To test whether variants in the TLR4 gene are associated with late-onset AD (LOAD), we organized a multicenter study of 785 subjects (399 cases and 386 matched controls) in a Han Chinese population. Ten single nucleotide polymorphisms (SNPs) that span the TLR4 gene, from approximately 5 kb of the predicted 5’-untranslated region (UTR) to approximately 6 kb of the predicted 3’- UTR, were selected and their associations with LOAD risk factors were assessed. With respect to allelic diversity, the minor alleles of seven SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs7037117, and rs7045953) in TLR4 showed consistent protective effects against the risk of developing LOAD. With regard to genotypic diversity, individuals carrying at least one minor allele of each SNP above had a consistently lower risk of LOAD than those with no copies of the minor alleles (ORs ranging from 0.445 to 0.637). rs7045953, located in the 3’-UTR of TLR4, was most strongly associated with LOAD, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 1.7x10-6, Pc s1.0x10-4). Our data suggests that the TLR4 gene contributes to the susceptibility for LOAD in Han Chinese.
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Cite this article as:
Jin-Tai Yu, Dan Miao, Wei-Zhen Cui, Jiang-Rong Ou, Yan Tian, Zhong-Chen Wu, Wei Zhang, Lan Tan , Common Variants in Toll-Like Receptor 4 Confer Susceptibility to Alzheimer’s Disease in a Han Chinese Population, Current Alzheimer Research 2012; 9 (4) . https://dx.doi.org/10.2174/156720512800492495
DOI https://dx.doi.org/10.2174/156720512800492495 |
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
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