The Correlational Research Between IL-4 Gene Methylation And The Pathogenesis Of Recurrent Aphthous Ulcer

Objective:To investigate whether the methylation patterns of the interleukin-4?IL-4?gene promoter in the peripheral blood of recurrent aphthous ulcer?RAU?patients were changed.Methods:20 patients?RAU group?diagnosed with RAU were included in the oral clinic of the first clinical medical college of shanxi medical university from May 2018 to May 2019,including 12 females and 8 males,with an average age of 27.2±6.2 years.During the same period,20 healthy volunteers matching the age and gender of the case group were selected from the medical personnel of our hospital as the control group,including 11females and 9 males,with an average age of 27.4±4.8 years.After DNA was modified with sodium bisulfite,the IL-4 promoter methylation level was analyzed by direct sequencing.The IL-4 mRNA level was detected by real-time quantitative PCR.Results:The IL-4 gene promoter fragment contained 10 CPG sites from-1400bp to-1625bp.The methylation rates of CPG^-1556?CPG^-1483?CPG^-14791479 and 10 CPG sites were significantly higher in RAU group?32.0±19.9%,53.0±13.4%,46.0±19.8%,39.3±12.4%?than in healthy control group?20.0±3.2%,35.5±12.3%,28.0±14.4%,32.6±5.8%?,with statistically significant differences?P=0.015,P=0.000,P=0.002,P=0.038?.The relative expression of IL-4 mRNA in the peripheral blood of RAU patients?1.0±0.1?was significantly lower than that of the healthy control group?1.5±0.2?,with statistically significant difference?P<0.001?.There was a significant negative correlation between the average methylation rate of IL-4 gene promoter and the relative expression level of IL-4 mRNA in RAU group?r=-0.494,P=0.027?.In the multivariate analysis,smoking,vitamin B12 and folic acid in the RAU group were significantly correlated with the mean methylation rate of the IL-4 gene promoter?P<0.001,P=0.004,P=0.007?.Conclusion:The hypermethylation of IL-4 promoter in RAU patients may be related to redution of IL-4 gene transcription.Vitamin B12,folic acid and smoking may have an effect on IL-4 gene methylation in peripheral blood of RAU patients.