Paria Motahari - Assistant Professor, Department of Oral Medicine, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
Fatemeh Pournaghi-Azar - Assistant Professor, Department of Restorative Dentistry, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
Pooya Khodadadi - Student of Dentistry, Department of Oral Medicine, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

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 ۲۰۰۰ to December ۲۰۱۹. 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 I۲ tests were used to evaluate statistical heterogeneity between the studies.RESULTS: Amongst the ۶۱۹ articles obtained in the first stage of our search of database, ۲۱ 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 -۳۰۸ G/A had protective effects for RAS [odds ratio (OR) = ۰.۳۹۲, ۹۵% confidence interval (CI) = ۰.۱۴۵-۱.۰۶۱, P = ۰.۰۴۵].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.

Tumor Necrosis Factor-Alpha, Polymorphism, Single Nucleotide, stomatitis, Aphthous