Bone Abstracts

Toll-like receptors (TLRs) appear to be involved in the pathogenesis of osteoarthritis (OA) and recent studies have suggested that polymorphisms in TLR9, an endosomal TLR are associated with knee OA in at least one population. TLR3 is also found on the surface of endosomes where they respond primarily to nucleic acid based pathogen-associated molecular patterns (PAMPs) from viruses and bacteria. We therefore determined the predictive value of TLR3 gene polymorphisms and further functional study on knee OA in a Han Chinese population. Two separate populations were studied in a two stage case–control study with a total of 823 OA cases and 594 healthy controls. Four single nucleotide polymorphisms (SNPs) of TLR genes were evaluated by PCR–RFLP assays. Real-time PCR were performed to test the functional expression of the identified promoter polymorphism following dexamethasone stimulation. An association with polymorphisms at rs3775296 and rs3775290 of TLR3 and knee OA was identified in both populations. The ATCA haplotype of TLR3 was associated with a decreased risk of OA CTCA and CCTA haplotypes were associated with an increased susceptibility. We also found a significant difference in the expression of TLR3 by dexamethasone treatment among the various genotypes of rs3775296 (P<0.001). Our findings indicate that a SNP in the promoter region of TLR3 is associated with elevated TLR3 mRNA level and with susceptibility to knee OA in the Han Chinese population.