Toll-like receptor polymorphisms and rheumatoid arthritis: a systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and influence the clinical characteristics of RA. The authors conducted a systematic review on associations between TLR polymorphisms and RA susceptibility and clinical findings. Meta-analysis was performed if at least three comparisons of an issue were available. A total of 14 studies were included in this systematic review, which included European and Asian studies. Meta-analysis of five European studies showed no association between the TLR4 Asp299Gly (rs4986790) polymorphism and RA (OR for the minor allele = 0.907, 95 % CI = 0.755-1.088, p = 0.291). Furthermore, none of these studies found any association between the polymorphism and clinical characteristics. A significant difference between TLR9 rs187084 allele frequencies in RA patients and controls was found in one Turkish study (p = 0.003), and a moderate association between RF positivity and TLR8 rs5741883 was found in an European study (p = 0.001). The numbers of guanine-thymine [(GT)(n)] repeats in intron II of the TLR2 gene were found a significantly higher S-allele frequency in Korean patients with RA than in controls (30.3 vs. 23.0 %, p = 0.03). This meta-analysis shows lack of an association between the TLR4 Asp299Gly polymorphism and RA. However, our finding suggests the possibility that TLR polymorphisms are associated with the development and clinical characteristics of RA. Because of a paucity of data of the TLR polymorphisms, case-control studies are required to determine whether TLR2, 4, 8, 9 polymorphisms contribute to RA susceptibility or severity in more than 2,000 patients and controls.