title: Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease.
abstract: 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 (p(interaction) = 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.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. karenchen@ntu.edu.tw
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wen
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chu
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000378:metabolism; D016022:Case-Control Studies; D003704:Dementia / Q000175:diagnosis / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation; D008297:Male; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D011795:Surveys and Questionnaires; D013624:Taiwan; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D051197:Toll-Like Receptor 4