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

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-1ß-511, IL-1ß+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-1ß-511 in dominant 0.69(0.50-0.95) and overdominant 0.73(0.55-0.96) models, IL-1ß+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-1ß-511(C/T), IL-6-174(G/C), and IL-1ß+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.

Interleukin-4 and Interleukin-4 Receptor Alpha Gene Polymorphisms in Recurrent Aphthous Stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral condition with a major impact on the quality of life. The condition is thought to be due to the overexpression of T helper-1(Th1)-related cytokines. Since interleukin-4 (IL-4) and its receptor (IL-4Rα) are antagonistic to Th-1 pathways, polymorphisms in their genes may also be involved in the pathogenesis of aphthous stomatitis. METHODS: Sixty-four patients diagnosed with minor RAS and 141 (age- and sex-matched) healthy controls were assessed for 3 single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-4 gene (-1098G/T, -590C/T, and -33C/T), and 1 SNP in IL-4Rα gene (+1902 A/G). RESULTS: No significant differences were detected between the patient and the control group regarding IL-4 allele frequencies. However, the patient group demonstrated a higher frequency of IL-4 -590 CC genotype and a lower rate of IL-4 -590 TC genotype. The TCT, GTT, GCT, and GTC haplotypes of the IL-4 gene (-1098, -590, -33) were significantly more frequent in the patients and the GCC, and TTT haplotypes were more common in healthy controls. No significant differences were found in IL-4Rα gene polymorphism between the 2 groups. CONCLUSIONS: Certain polymorphisms of IL4 gene could predispose individuals to RAS.

An Update on Drug-induced Oral Reactions.

Adverse drug reactions (ADRs) are one of the major culprits in the development of oral lesions, which can be misdiagnosed with underlying diseases. The goal of this study is to summarize and update the current knowledge about drug-induced oral reactions. Electronic searches were performed in Scopus, Google Scholar, Cochrane and PubMed databases, for articles published between January 2008 and August 2017. Two authors screened the titles and abstracts for eligibility. Finally, 56 studies included in this review. There was no systematic homogeneity in the included studies; thereby no meta-analysis was performed. The most frequent oral ADR was xerostomia,andthe most reported cause was antihypertensive medications. Cardiovascular drugs were the most reported culprit agents for induction of oral ulcerative and vesiculo-bullous lesions, followed by methotrexate. Nonsteroidal anti-inflammatory drugs (NSAIDs) and ß-blockers were found the most common responsible drugs for induction of oral lichen planus. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Successful Implant Placement in a Case of Florid Cemento-Osseous Dysplasia: A Case Report and Literature Review.

Florid cemento-osseus dysplasia (FCOD) has been described as a reactive process in which normal bone is replaced by fibrous connective tissues and cementum-like materials. Radiographically it appears as dense, lobulated masses, often occurring bilaterally with symmetric involvement. In this case report, a successful implant placement has been reported in a 62-year-old Caucasian woman with a chief complaint of mandibular partial edentulous. Radiographic images showed the bilateral radiopaque lesions in edentulous regions of mandible, and mandibular anterior teeth alike. All mandibular teeth were vital and no root resorption was detected. The findings of X-ray images were attributable to FCOD. A highly conservative step-by-step 2-stage implant surgery was performed. After 6 months the implants loaded with fixed prosthesis. 2, 4, 6, 12, and 18 months after the surgery radiographic images were taken, which revealed an optimal functional rehabilitation and complete integration of implants. This report confirms that treating the edentulous area near the FCOD lesions could be planned, if conservative step- by-step implant placement been considered. To the best of our knowledge, a case of FCOD with successful implant placement has not been reported previously. More studies in more patients are needed to confirm results of such a therapeutic modality.

Interleukin-2, Interferon-gamma Gene Polymorphisms in Recurrent Aphthous Stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative inflammatory disease with unknown etiology. IL-2 and IFN-γ are secreted by Th1 cells and the elevated levels of them have been reported in RAS. Single nucleotide polymorphisms (SNPs) of IL-2 and IFN-γ genes could alter the cytokine production. The aim of this study was to investigate frequencies of IL-2 and IFN-γ alleles and genotypes in a group of patients with minor-RAS (MiRAS). PCR-SSP method used to type genomic DNA of 64 Iranian patients with MiRAS for IL-2 gene (G -330 T) and (G +166 T) and IFN-γ gene at position UTR5644 (A/T). Frequency of each allele and genotype was compared with control group. IL-2 +166 G allele was significantly lower among patients which was reflected in significantly decreased of GG genotype at this position, while IL-2 +166 T allele was significantly higher among patients, IL-2 GT genotype was also significantly higher in RAS patients. No significant differences were found regarding IL-2 -330 G/T allele frequencies, while IL-2 GT genotype at this position was significantly higher among patients and IL-2 -330 TT genotype was significantly lower among RAS patients. Although no significant differences were found in IFN-γ allele frequencies at UTR5644 (A/T), AT genotype at this position was significantly overrepresented among patients compared with controls. Results of this study suggest that certain SNPs of IL-2 and IFN-γ genes have association with predisposition of individuals to RAS. More studies in different ethnic groups are needed to confirm results of this study.

Immunotherapy of cancers comes of age.

INTRODUCTION: Cancer immunotherapy has evolved and is aimed at generating the efficacious therapeutic modality to enhance the specificity and power of the immune system to combat tumors. Areas covered: Current efforts in cancer immunotherapy fall into three main approaches. One approach is through the blockade of immune checkpoints, another approach is through adoptive cellular therapy, and the last approach is through vaccination. The goal of this review is to summarize the current understanding and status of cancer immunotherapy in these three categories. Expert commentary: We foresee the development of therapeutic protocols combining these approaches with each other or conventional therapies to achieve the most appropriate guideline for management of cancer.

Association of Transforming Growth Factor-Beta Gene Polymorphisms in Recurrent Aphthous Stomatitis.

This study has been conducted to evaluate the allele, genotype and haplotype frequencies of the polymorphic gene coding TGF-ß in recurrent aphthous stomatitis (RAS). TGF-ß gene typing was done by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. Allele frequencies were estimated by direct gene counting. C allele at codon 25 was significantly increased, while G allele at this position was significantly decreased in patients compared to the controls. A significantly higher frequency of CG genotype at codon 25 was found in control group. CC genotype and TT genotype at codon 10 of the gene was significantly decreased, while CT genotype at the same position was significantly increased in patients, indicating that CT heterozygosity at codon 10 TGF-ß is associated with greater risk of RAS. CG and TG haplotypes were significantly decreased while CC and TC haplotypes were significantly increased in patients compared with controls. This study indicates the TGF-ß single nucleotide polymorphisms could play a role in RAS pathogenesis. Thereby certain SNPs of TGF-ß gene have an association with RAS pathogenesis.

Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A -1082, C/T -819, and C/A -592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group. A significantly higher frequencies of the T allele at position -819 (p=0.006) and the A allele at position of -592 (p<0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position -1082 (p=0.007), CA genotype at position -592 (p=0.001), and CT genotype at position -819 (p=0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study.