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.Findings: 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 ε{lunate}4 status by logistic regression analysis (P = 0.035). Our result showed significant evidence of the interaction of ApoE ε{lunate}4 with rs187084. When we further stratified our data by the ApoE ε{lunate}4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ε{lunate}4 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.Conclusion: Our findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population. © 2013 Wang et al.; licensee BioMed Central Ltd.