title: Common variants in toll-like receptor 4 confer susceptibility to Alzheimer's disease in a Han Chinese population.
abstract: Toll-like receptor 4 (TLR4) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located within the previous identified linkage region of AD on chromosome 9q, and functionally is involved in the microglia-mediated inflammatory response, amyloid-β (Aβ) plaque formation and Aβ clearance. To test whether variants in the TLR4 gene are associated with late-onset AD (LOAD), we organized a multicenter study of 785 subjects (399 cases and 386 matched controls) in a Han Chinese population. Ten single nucleotide polymorphisms (SNPs) that span the TLR4 gene, from approximately 5 kb of the predicted 5'-untranslated region (UTR) to approximately 6 kb of the predicted 3'- UTR, were selected and their associations with LOAD risk factors were assessed. With respect to allelic diversity, the minor alleles of seven SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs7037117, and rs7045953) in TLR4 showed consistent protective effects against the risk of developing LOAD. With regard to genotypic diversity, individuals carrying at least one minor allele of each SNP above had a consistently lower risk of LOAD than those with no copies of the minor alleles (ORs ranging from 0.445 to 0.637). rs7045953, located in the 3'-UTR of TLR4, was most strongly associated with LOAD, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 1.7x10-6, Pc s1.0x10-4). Our data suggests that the TLR4 gene contributes to the susceptibility for LOAD in Han Chinese.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, PR China. yu-jintai@163.com
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
authors.forename: Wei-Zhen
authors.initials: WZ
authors.lastname: Cui
authors.forename: Jiang-Rong
authors.initials: JR
authors.lastname: Ou
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
authors.forename: Zhong-Chen
authors.initials: ZC
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4