The Genetic Association Between TLR-1, -2, -4, and -6 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility in a Chinese Han Population.

Abstract

Aims: The toll-like receptor (TLR) genes were shown to be involved in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the genetic associations between the TLR-1, -2, -4, and -6 genes polymorphisms with RA susceptibility in a Chinese Han population. Methods: Six polymorphisms [TLR-1 (rs5743610, rs5743618), -2 (rs5743708), -4 (rs4986790, rs4986791), and -6 (rs5743810)] in TLRs genes were genotyped in 360 patients with RA and 560 matched healthy controls by direct sequencing. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated using a standard logistic regression analysis. Results: No significant associations were observed under the allelic, dominant, or recessive models for TLR-1 rs5743610, TLR-2 rs5743708, TLR-4 rs4986790 and rs4986791, and TLR-6 rs5743810 polymorphisms and RA risk (all p > 0.05). However, significant associations were detected under the allelic, dominant, and recessive models for TLR-1 rs5743618 and RA risk (allelic: OR [95% CI] = 2.21 [1.73-2.81], p < 0.0001; dominant: OR [95% CI] = 2.33 [1.75-3.09], p < 0.0001; recessive models: OR [95% CI] = 3.70 [1.85-7.41], p = 0.0002). In addition, TLR6 rs5743810 was found to be associated with the rheumatoid factor (RF)- and anticyclic citrullinated peptide (anti-CCP)- antibody in RA group (RF: OR [95% CI] = 2.29 [1.42-3.69], p = 0.0007; anti-CCP: OR [95% CI] = 2.33 [1.39-3.89], p = 0.001). Conclusions: The allelic, dominant, and recessive models of TLR1 rs5743618 might be associated with RA susceptibility. Also, the TLR6 rs5743810 marker may be associated with RF and the anti-CCP antibody of RA in the Chinese Han population.