{'fraction_non_alphanumeric': 0.06735469853340575, 'fraction_numerical': 0.0755024443237371, 'mean_word_length': 5.079207920792079, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
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 ~ 0.96) and dominant model (OR = 0.74, 95% CI 0.56 ~ 0.99) of Asp299Gly polymorphism. A trend of reduced risk was also observed under the heterozygous model (OR = 0.77, 95% CI 0.58 ~ 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 ~ 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.