Association of a functional polymorphism in the promoter region of TLR-3 with osteoarthritis: A two-stage case-control study

Hsin Yi Yang, Herng Sheng Lee, Chian Her Lee, Wen Hui Fang, Hsiang Cheng Chen, Donald M. Salter, Sui Lung Su

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)680-685
Number of pages6
JournalJournal of Orthopaedic Research
Volume31
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • functional polymorphism
  • osteoarthritis
  • toll-like receptor

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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