title: Toll-like receptor 9 promoter polymorphism is associated with decreased risk of Alzheimer's disease in Han Chinese.
abstract: BACKGROUND
  Toll-like receptors (TLRs), as major innate immune mediators, may be involved in clearance of cerebral amyloid-β (Aβ) deposits. Recently, a novel TLR9 signaling pathway has been uncovered, which is functionally associated with the immune inflammatory response and reducing Aβ burden in Alzheimer's disease (AD) mice. Therefore, TLR9 might represent a reasonable functional candidate gene for AD.
  
  
  RESULTS
  Our study investigated 1,133 sporadic late-onset AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han Chinese population. One selected functional rs187084 polymorphism within the TLR9 gene was genotyped by polymerase chain reaction-ligase detection reaction in a case-control associated study. The TLR9 rs187084 variant homozygote GG was significantly associated with a decreased LOAD risk after adjusting for age, gender, and ApoE ε4 status by logistic regression analysis (P = 0.035). Our result showed significant evidence of the interaction of ApoE ε4 with rs187084. When we further stratified our data by the ApoE ε4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ε4 carriers (P < 0.001, P = 0.003, respectively). Moreover, we examined TLR9 expression in peripheral blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084 polymorphism was associated with a higher TLR9 expression than two other genotypes in LOAD patients.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.
authors: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors: Ying-Li
authors: YL
authors: Wang
authors: Meng-Shan
authors: MS
authors: Tan
authors: Jin-Tai
authors: JT
authors: Yu
authors: Wei
authors: W
authors: Zhang
authors: Nan
authors: N
authors: Hu
authors: Hui-Fu
authors: HF
authors: Wang
authors: Teng
authors: T
authors: Jiang
authors: Lan
authors: L
authors: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
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