Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.

<h4>Background</h4>Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer's disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and...

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Autores principales:	Yen-Ching Chen, Ping-Keung Yip, Yi-Ling Huang, Yu Sun, Li-Li Wen, Yi-Min Chu, Ta-Fu Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b743d2452eeb47639726d098106cb875
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spelling	oai:doaj.org-article:b743d2452eeb47639726d098106cb8752021-11-18T08:04:43ZSequence variants of toll like receptor 4 and late-onset Alzheimer's disease.1932-620310.1371/journal.pone.0050771https://doaj.org/article/b743d2452eeb47639726d098106cb8752012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23272070/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer's disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients.<h4>Methods</h4>A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007-2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population.<h4>Results</h4>Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30-4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36-0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14-0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (p(interaction) = 0.01). These associations remained significant after correction for multiple tests.<h4>Conclusions</h4>Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7.Yen-Ching ChenPing-Keung YipYi-Ling HuangYu SunLi-Li WenYi-Min ChuTa-Fu ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50771 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yen-Ching Chen Ping-Keung Yip Yi-Ling Huang Yu Sun Li-Li Wen Yi-Min Chu Ta-Fu Chen Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
description	<h4>Background</h4>Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer's disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients.<h4>Methods</h4>A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007-2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population.<h4>Results</h4>Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30-4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36-0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14-0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (p(interaction) = 0.01). These associations remained significant after correction for multiple tests.<h4>Conclusions</h4>Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7.
format	article
author	Yen-Ching Chen Ping-Keung Yip Yi-Ling Huang Yu Sun Li-Li Wen Yi-Min Chu Ta-Fu Chen
author_facet	Yen-Ching Chen Ping-Keung Yip Yi-Ling Huang Yu Sun Li-Li Wen Yi-Min Chu Ta-Fu Chen
author_sort	Yen-Ching Chen
title	Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
title_short	Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
title_full	Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
title_fullStr	Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
title_full_unstemmed	Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
title_sort	sequence variants of toll like receptor 4 and late-onset alzheimer's disease.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b743d2452eeb47639726d098106cb875
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Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.

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