Associations of IL-1, 6, and 10 Gene Polymorphisms with Susceptibility to Recurrent Aphthous Stomatitis: Insights from a Meta-Analysis

Objective. To investigate the DNA methylation using pyrosequencing and its effects on the upregulation of IL6 mRNA in patients with recurrent aphthous stomatitis (RAS) in connection with hematinic deficiency and atopy. Material and Methods. This cross-sectional study was conducted at Dr. Hasan Sadikin Hospital, Bandung, from January–March 2019 and was approved by the Health Research Ethics Committee of Universitas Padjadjaran (Ethics No. 990/UN6.KEP/EC/2018). Furthermore, the subjects had RAS ulcers with a history of at least twice a year along with atopy and dietary imbalance with no history of recurrent intraoral herpes or any systemic diseases. This study was performed on 23 RAS patients and 21 healthy subjects, and the sampling was carried out consecutively. The blood samples were collected from all the subjects, and then, the DNA and RNA were extracted from the peripheral blood mononuclear cells (PBMCs). Consequently, the bisulfite-modified DNA was used to confirm the methylation status of the IL6 gene promoter through the pyrosequencing method. The methylation levels of the IL6 promoter were assessed by a reverse transcriptase-polymerase chain reaction technique. The gene expression of RAS and the control group was analyzed by the 2−ΔΔCT method. The statistical analysis using the Mann–Whitney U test was conducted to evaluate IL6 mRNA levels and DNA methylation with p value <0.05 considered to be statistically significant. Result. The IL6 mRNA levels were approximately 1.88-fold in RAS patients, and there was a significant relationship between the expression of the IL6 gene and the increased risk of RAS p < 0.001 . It was reported that four out of six sites in the cytosine phosphate guanine (CpG) island IL6 promoter had a lower degree of methylation, and two other sites in patients with RAS had greater methylation compared with control, but not statistically significant. Conclusion. This study showed the upregulation of IL6 mRNA levels in RAS patients compared to control. DNA methylation in the present study is at sites 566–658, whereas the location of the IL6 promoter is at sites 1–1684. Thus, it would be necessary conducting some research at other CpG sites of IL6 promoter islands to determine the status of DNA methylation.

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“…Many inflammatory mediators, including IL-1, IL-2, IL-17, and IL-18, have been investigated in RAS [17,54,55].…”

Section: Discussionmentioning

confidence: 99%

The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients

Nur’aeny

Gurnida

Suwarsa

et al. 2021

International Journal of Dentistry

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“…Sustained and excessive IL‐6 production can disrupt the cytokine network and lead to oral mucosal damage, which eventually leads to mucosal lesions in RAS. In recent years, more studies on IL‐6 had turned to gene polymorphism, several meta‐analysis showed that the IL‐6‐174 G/C polymorphism did not have a statistically significant association with RAS susceptibility, 14,15 whereas there was also a study showed individuals with the G allele and GG genotype of IL‐6‐174 appeared to be more vulnerable to developing RAS 16 . Therefore, the role of IL‐6 and IL‐17A in RAS remains to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin‐6, interleukin‐17A, and tumor necrosis factor‐alpha in patients with recurrent aphthous stomatitis

Shen

Gong

et al. 2021

J Oral Pathology Medicine

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Background Recurrent aphthous stomatitis remains the most common disease of the oral mucosa. The aim of this study was to investigate the clinical significance of serum interleukin‐6, interleukin‐17A, and tumor necrosis factor‐alpha in recurrent aphthous stomatitis. Methods Using flow cytometry analysis, we detect the level of serum interleukin‐2, interleukin‐6, interleukin‐17A, tumor necrosis factor‐alpha, and interferon‐gamma in 127 patients with recurrent aphthous stomatitis and 20 healthy control cases; compare; and analyze the correlation of each index. Results The levels of serum interleukin‐2, interleukin‐6, tumor necrosis factor‐alpha, and interferon‐gamma in the recurrent aphthous stomatitis group were higher than in the control group, and the differences were statistically significant (P < .05). There was no significant difference in interleukin‐17A between the two groups. Conclusion The levels of serum interleukin‐6 and tumor necrosis factor‐alpha in recurrent aphthous stomatitis patients were significantly increased. Considering that serum TNF‐α was mostly within the normal range, its role in the pathology of RAS needed to be further explored.

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“…The choice of these pro-inflammatory cytokines was confirmed by many studies that investigated the clinical significance of serum IL-6, IL-1, and TNF-α in RAS. [ 6 23 , 24 ] Results of these studies revealed that the levels of serum IL-1, IL-6, and TNF-α in RAS patients were significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Novel Topical Camel Whey Protein Gel for the Treatment of Recurrent Aphthous Stomatitis

Elamrousy

Mortada

Shoukheba

2021

Journal of International Society of Preventive and Community Dentistry

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Associations of IL-1, 6, and 10 Gene Polymorphisms with Susceptibility to Recurrent Aphthous Stomatitis: Insights from a Meta-Analysis

Abstract: The IL-1b+3954 C/T polymorphism significantly increases RAS risk. In addition, the IL-10-1082 G/A polymorphism provided protective effects for RAS in the Asian population.

Cited by 12 publications

References 34 publications

The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients

The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients

Serum interleukin‐6, interleukin‐17A, and tumor necrosis factor‐alpha in patients with recurrent aphthous stomatitis

Evaluation of Novel Topical Camel Whey Protein Gel for the Treatment of Recurrent Aphthous Stomatitis

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