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Background

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.

Methods

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.

Results

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 pinteraction = 0.01. These associations remained significant after correction for multiple tests.

Conclusions

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.



Autor: Yen-Ching Chen , Ping-Keung Yip, Yi-Ling Huang, Yu Sun, Li-Li Wen, Yi-Min Chu, Ta-Fu Chen

Fuente: http://plos.srce.hr/



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