Association of two polymorphisms Asp299Gly and Thr399Ile in Toll-like receptor 4 with rheumatoid arthritis: A meta-analysis

Our meta-analysis aims to evaluate the association of Asp299Gly and Thr399Ile with rheumatoid arthritis (RA) susceptibility and severity. By manually searching 3 electronic databases (PubMed, Embase and Web of Science), relevant articles were collected. After checking eligibility for every study, this meta-analysis on eligible studies was performed under 5 genetic models: (1) allelic contrast; (2) heterozygous model; (3) homozygous model; (4) dominant model; (5) recessive model. In Spanish populations, a significantly decreased RA risk was identified in allelic comparison (odds ratio [OR] = 0.73, 95% CI 0.55 similar to 0.96) and dominant model (OR = 0.74, 95% CI 0.56 similar to 0.99) of Asp299Gly polymorphism. A trend of reduced risk was also observed under the heterozygous model (OR = 0.77, 95% CI 0.58 similar to 1.03). As for Thr399Ile, it might also have a protective effect on Spanish populations in allelic comparison (OR = 0.71, 95% CI 0.44 similar to 1.15). In contrast, for both Asp299Gly and Thr399Ile, a higher risk of RA was detected in Chinese Han populations. The frequency of both Asp299Gly and Thr399Ile increased in rheumatoid factor (RF)-positive subjects in Chinese patients (Asp299Gly, RF+:RF- = 0.165:0.145; Thr399Ile, RF+:RF- = 0.170:0.161) and decreased in Spanish patients (Asp299Gly, RF+:RF- = 0.060:0.073; Thr399Ile, RF+:RF- = 0.046:0.056), but not to a statistically significant extent. Our meta-analysis suggested that both Asp299Gly and Thr399Ile might have a protective effect on Spanish populations, but the 2 polymorphisms could act as a susceptible factor in Chinese Han populations. To confirm our results, further investigation concerning the functional impacts of Asp299Gly and Thr399Ile are still needed.