Role of genetic polymorphisms in recurrent aphthous stomatitis: A systematic review and meta-analysis

Cytokine. 2022 May:153:155864. doi: 10.1016/j.cyto.2022.155864. Epub 2022 Mar 18.


Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with unknown etiology. Identifying the genetic markers can improve medical care and prevention of RAS. Genetics variants inflammatory agents are associated with the risk of RAS. Thus, this meta-analysis aimed to investigate the genetic polymorphisms in RAS. Electronic literature search was carried out on Scopus, PubMed, and Web of Science (WOS). The references of relevant reviews were also manually checked. The observational studies till the end of 2020 were included. Odds ratio (OR) was estimated by fixed and random effect model. Seventeen polymorphisms in 23 studies were included in analysis. Pooled analysis performed for 12 polymorphisms (IL-2+166, IL-2-330, IL-4-590, IL-4 RA1902, IL-6-597, TNF-α-308, NLRP3(rs4612666, rs10754558), MMP2- rs2285053, MMP9- rs11697325, MMP9- rs3918242, MMP9- rs17576, IL-1a-889, IL-10-819, and IL-12+1188). The meta-analyses carried out for six polymorphisms (IL-1β-511, IL-1β+3954, IL-6-174, IL-10-592, IL-10-1082, and serotonin transporter). There were following significant results for IL-10, 819 in allelic:1.46(1.04-2.05) and homozygote: 1.61(1.08-2.39) models, serotonin Transporter in allelic:0.53(0.40-0.71), recessive:0.56(0.35-0.90), dominant:0.35(0.22-0.57) and homozygote:0.30(0.17-0.54) models. IL-1β-511 in dominant 0.69(0.50-0.95) and overdominant 0.73(0.55-0.96) models, IL-1β+3954 in allelic 1.25(1.05-1.50), homozygote 1.67(1.05-2.63) and dominant 1.26(1.01-1.57) models, IL-6-174 in dominant 2.24(1.36-3.67), IL-10-592 in homozygote 0.41(0.23-0.72) and dominant 0.55(0.33-0.93), IL-10-1082 in allelic 1.19(1.01-1.39) and dominant 1.29(1.02-1.64). In conclusion, serotonin transporter(L/S), IL-10-819(T/C), IL-10-592(C/A), IL-10-1082(G/A), IL-1β-511(C/T), IL-6-174(G/C), and IL-1β+3954 (T/C) polymorphisms are associated with susceptibility to RAS. These variants could be potential predictors of RAS and could be used for the developing clinically effective genetic panel for RAS.

Keywords: Cytokine; Inflammation; Polymorphism; Recurrent aphthous stomatitis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-2 / genetics
  • Interleukin-4 / genetics
  • Interleukin-6 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Stomatitis, Aphthous* / genetics


  • Interleukin-2
  • Interleukin-6
  • Serotonin Plasma Membrane Transport Proteins
  • Interleukin-10
  • Interleukin-4
  • Matrix Metalloproteinase 9

Supplementary concepts

  • Sutton disease 2