title: Association of a functional polymorphism in the promoter region of TLR-3 with osteoarthritis: a two-stage case-control study.
abstract: Recent studies have suggested that polymorphisms in toll-like receptor 9 (TLR-9), an endosomal TLR, are associated with knee osteoarthritis (OA). TLR-3, -7, and -8 are also found on the surface of endosomes and to investigate whether similar associations exist with polymorphisms in these TLR genes we performed a two-stage case-control study and genotyped 11 TLR single nucleotide polymorphisms (SNPs) in 823 OA cases and 594 healthy controls by polymerase chain reaction restriction fragment length polymorphism assays. Real-time PCR was performed to assess the functional expression of an identified promoter polymorphism in TLR-3 following dexamethasone stimulation of articular chondrocytes. An association between TLR-3 SNPs at rs3775296 and rs3775290 and OA was identified in both populations. In males the allelic frequencies of TLR-7 rs179010 and TLR-8 rs5744080 were significantly different between OA cases and healthy controls. The ATCA, CTCA, and CCTA haplotypes of TLR-3 were associated with OA susceptibility. A significant difference in TLR-3 gene expression following dexamethasone treatment was seen among the various genotypes of rs3775296 (p = 0.004). Our findings indicate that a SNP in the promoter region of TLR-3 is associated with elevated TLR-3 gene expression and susceptibility to knee OA in a Chinese Han population.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Yang
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
authors.forename: Chian-Her
authors.initials: CH
authors.lastname: Lee
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Fang
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chen
authors.forename: Donald M
authors.initials: DM
authors.lastname: Salter
authors.forename: Sui-Lung
authors.initials: SL
authors.lastname: Su
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002356:Cartilage / Q000166:cytology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D051196:Toll-Like Receptor 3 / Q000235:genetics*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3