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

• Main Authors: Yang, Hsin-Yi, 楊昕禕
• Other Authors: Su, Sui-Lung
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/77342086322707575936

博士 === 國防醫學院 === 生命科學研究所 === 101 === Background Toll-like receptors (TLRs) appear to be involved in the pathogenesis of osteoarthritis (OA) and recent studies have suggested that polymorphisms in TLR-9, an endosomal TLR are associated with knee OA in at least one population. TLR-3, 7, and 8 are 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 TLR-3, 7, 8 gene polymorphisms and further functional study on knee OA in a Han Chinese population. Methods Two separate populations were studied in a two stage case-control study with a total of 823 OA cases and 594 healthy controls. Eleven single nucleotide polymorphisms (SNPs) of TLR genes were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Real-time PCR were performed to test the functional expression of the identified promoter polymorphism following dexamethasone stimulation. Results An association with polymorphisms at rs3775296 and rs3775290 of TLR-3 and knee OA was identified in both populations. In males the allelic frequencies of TLR-7 rs179010 and TLR-8 rs5744080 polymorphisms were significantly different between OA cases and healthy controls. The ATCA haplotype of TLR-3 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 TLR-3 by dexamethasone treatment among the various genotypes of rs3775296 (p = 0.004). Conclusions Our findings indicate that a SNP in the promoter region of TLR-3 is associated with elevated TLR-3 mRNA level and with susceptibility to knee OA in the Han Chinese population. TLR-7 and TLR-8 polymorphisms might lead to a gender-specific influence of the susceptibility to knee OA.