Role of tumor necrosis factor-alpha in pathogenesis of recurrent aphthous stomatitis: A systematic review and meta-analysis

BACKGROUND an‎d AIM: Recurrent aphthous stomatitis (RAS) is a lesion of the oral cavity with an unknown etiology. Several studies have been performed on the role of tumor necrosis factor-alpha (TNF-α) in RAS. The main purpose of this paper was to review TNF-α level and its gene polymorphism in patients with RAS, the factors influencing the production of TNF-α, and its role in RAS development. METHODS: In this review study, all articles containing English abstract were searched in the PubMed, Cochrane Library, and Scopus databases from January 2000 to December 2019. The searches were done using the Medical Subject Heading (MESH) terms and keywords of "recurrent aphthous stomatitis" or "recurrent aphthous ulcers" or "recurrent oral ulcers" and “tumor necrosis factor-alpha” or “TNF-α”. The data for gene polymorphism were analyzed using Comprehensive Meta-Analysis (CMA) software. Regarding the heterogeneity of studies, the random effects model was used. Cochran’s Q and I2 tests were used to evaluate statistical heterogeneity between the studies. RESULTS: Amongst the 619 articles obtained in the first stage of our search of database, 21 articles which were fitted to our study based on the entry/exit criteria were selected in the review. According to this meta-analysis, recessive model of TNF-α -308 G/A had protective effects for RAS [odds ratio (OR) = 0.392, 95% confidence interval (CI) = 0.145-1.061, P = 0.045]. CONCLUSION: The results showed the important role of TNF-α in RAS development. There are numerous factors involved in producing this cytokine. Identifying TNF-α production pathway and its effects in RAS formation is significant in developing new prevention and treatment methods.