Identification of the causal relationship between sleep quality, insomnia, and oral ulcers.

BACKGROUND: Multiple epidemiological studies have posited a potential association between sleep quality and the risk of oral diseases, yet the resulting conclusions have remained contentious, and the presence of a causal link remains equivocal. In this study, we aimed to investigate the causal relationship between sleep duration, insomnia, and common oral diseases. METHODS: We utilized genetic correlation and two-sample Mendelian randomization analyses based on summary statistics from genome-wide association studies of sleep duration (N = 460,099), insomnia (N = 462,341), mouth ulcer (N = 385,026), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652). RESULTS: Our results revealed a negative genetic correlation between sleep duration and mouth ulcer (genetic correlation: -0.09, P = 0.007), while a positive genetic correlation between insomnia and mouth ulcer was observed (genetic correlation: 0.18, P = 2.51E-06). Furthermore, we demonstrated that longer sleep duration is significantly associated with a reduced risk of mouth ulcers (OR: 0.67, 95% CI: 0.54-0.83, P = 2.84E-04), whereas insomnia is nominally associated with an increased risk of mouth ulcers (OR: 1.40, 95% CI: 1.01-1.95, P = 0.044). In contrast, no significant association was detected between sleep quality and periodontal disease or oral cavity cancer. CONCLUSIONS: This work provides robust evidence to support the notion that enhanced sleep quality may confer a decreased risk of oral ulcers, thereby bearing considerable clinical relevance.

Mosaic Small Supernumerary Marker Chromosome Derived from Five Discontinuous Regions of Chromosome 8 in a Patient with Neutropenia and Oral Aphthous Ulcer.

Small supernumerary marker chromosomes (sSMCs) are characterized as additional centric chromosome fragments which are too small to be classified by cytogenetic banding alone and smaller than or equal to the size of chromosome 20 of the same metaphase spread. Here, we report a patient who presented with slight neutropenia and oral aphthous ulcers. A mosaic de novo sSMC, which originated from 5 discontinuous regions of chromosome 8, was detected in the patient. Formation of the sSMC(8) can probably be explained by a multi-step process beginning with maternal meiotic nondisjunction, followed by post-zygotic anaphase lag, and resulting in chromothripsis. Chromothripsis is a chromosomal rearrangement which occurs by breakage of one or more chromosomes leading to a fusion of surviving chromosome pieces. This case is a good example for emphasizing the importance of conventional karyotyping from PHA-induced peripheral blood lymphocytes and examining tissues other than bone marrow in patients with inconsistent genotype and phenotype.

Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

The prevalence of Behçet's disease in the north of Jordan: a hospital-based epidemiological survey.

OBJECTIVES: To estimate the prevalence of Behçet's disease (BD) in Jordan, with the additional aim of comparing this prevalence among hospital workers in other geographical areas. METHODS: In the first stage of our survey, 2,569 employees from 6 hospitals in north Jordan were interviewed using a screening questionnaire to identify individuals with recurrent oral ulcers (ROU), a previous diagnosis of BD (PDBD) and/or any major symptom related to BD. In the second stage, all individuals with ROU or PDBD identified at stage 1, were examined by 2 rheumatologists for the presence/confirmation of BD according to the International Study Group (ISG) criteria. Pathergy test was performed according to recommendations. RESULTS: ROU were present in 210 (8.2%) individuals. BD was confirmed in 10 employees with PDBD. Seven more BD patients were found. Mean age of 17 BD patients was 38.6±10.7 (range 26-65 y). M: F was 2.4:1. Pathergy test was positive in 8/17. A family history of ROU or BD was noted in 9 (52%) and 3 (25.0%), respectively, compared to 227 (8.9%) and 62 (2.6%) in the whole group, excluding the BD patients (p<0.001 and 0.008, respectively). The prevalence rate of BD in the north of Jordan was estimated as 66:10.000 (95% CI 34.8 to 97.5:10000). CONCLUSIONS: The results of this first ever survey indicated that the prevalence of BD in the north of Jordan is among the highest in the world. This prevalence can now be compared to hospital workers in other geographical areas.

Association between interleukin gene polymorphisms and risk of recurrent oral ulceration.

We conducted a case-control study to investigate the association between the functional IL-1ß+3954 (C/T), IL-6-174 (G/C), IL-10-1082 (G/A), and IL-10-819C/T genetic polymorphisms and risk of recurrent oral ulceration (ROU) in a Chinese population. Polymorphisms of IL-1ß+3954C/T, IL-6-174G/C, IL-10-1082A/G and IL-10-819C/T were assessed by polymerase chain reaction-restriction fragment length polymorphism. The genotype distributions of the IL-1ß+3954 C/T and IL-10-819C/T were in Hardy-Weinberg equilibrium in the control group. Conditional logistic regression analyses showed that subjects carrying the IL-1ß+3954CC and IL-10-1082AA genotypes had a significantly increased risk of ROU, with adjusted ORs (95%CI) of 2.86 (1.37-6.33) and 1.72 (1.02-2.89), respectively. In summary, we found that IL-1ß+3954C/T and IL-10-1082A/G polymorphisms are associated with an increased risk of ROU.

Association of MTHFR gene C677T mutation with recurrent aphthous stomatitis and number of oral ulcers.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Methylenetetrahydrofolate reductase (MTHFR) gene variants are associated with thrombophilia and vasculopathy that may result in oral ulceration. Oral ulcers are also the most common feature of Behcet's disease (BD). Association of MTHFR gene C677T mutation with BD has been reported in different populations. The aim of the present study was to investigate the possible association between MTHFR gene C677T mutation and RAS and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients. MATERIALS AND METHODS: The study included 188 patients affected by RAS and 200 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation. RESULTS: The genotype and allele frequencies of C677T mutation showed statistically significant differences between RAS patients and controls (p = 0.002 and p = 0.0004, respectively). After stratifying RAS patients according to clinical characteristics of oral ulcers, a significant association was observed between C677T mutation and number of oral ulcers of RAS patients (p = 0.006). CONCLUSIONS: As a result, a high association between MTHFR gene C677T mutation and RAS was observed in the present study. Also number of oral ulcers was found to be associated with MTHFR C677T mutation in RAS patients. CLINICAL RELEVANCE: If our observation can be substantiated with further studies, evaluation for MTHFR mutations and perhaps folate supplementation may become necessary in selected patients.

Causal associations between estradiol and mouth ulcers: A Mendelian randomization study.

People have difficulty in eating and speaking when they are suffering from mouth ulcers. Some studies suggest that estradiol is associated with the development and treatment of mouth ulcers, while some do not. To clarify the effect of estradiol on mouth ulcers, we performed 2-sample Mendelian randomization and multivariable Mendelian randomization (MVMR) analysis to evaluate their relationship. Data were obtained from the IEU OpenGWAS project and UK biobank, including male estradiol dataset (case/controls = 13,367/134,323), female estradiol dataset (case/controls = 37,461/126,524), mouth ulcers dataset (case/controls = 47,102/414,011). The causal associations were estimated by MR-Egger, weighted median, inverse-variance weighted (IVW) method, simple mode, and weighted mode. Cochran Q test, MR-Egger intercept test, MR-PRESSO tests, and leave-one-out analysis were used to examine sensitivity analyses. The MVMR controlling for depression, anxiety or panic attacks, severe stress and adjustment disorders was used to assess the effect of estradiol on mouth ulcers. Through screening, 13 single nucleotide polymorphisms (SNPs) of males and 2 SNPs of females in estradiol were used for harmonizing and MR analysis. The 2-sample MR analysis showed no causal association between estradiol of males and mouth ulcers (IVW, OR: 0.998, 95% confidence interval [95% CI]: 0.995-1.001, P = .18). Similar results were obtained between estradiol of females and mouth ulcers (IVW, OR: 1.000, 95% CI: 0.988-1.012, P = .97). No pleiotropy and heterogeneity were found and the results were robust (P > .05). After adjusting for the potential effects of confounders, estradiol of males and mouth ulcers still showed no causal association through MVMR analysis (P = .081). While MVMR analysis showed that the causal relationship between estradiol and mouth ulcers in women could not be statistical for the small number of SNPs. There was no evidence of a causal relationship between estradiol and mouth ulcers. The strategy of treating mouth ulcers with estradiol still needs to be confirmed by more studies.

Integrating GWAS and proteome data to identify novel drug targets for MU.

Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.

A genome-wide association analysis: m6A-SNP related to the onset of oral ulcers.

Oral ulcers are one of the most common inflammatory diseases on oral mucosa that have obvious impacts on patients. Studies have shown that N6-methyladenosine (m6A) RNA transcription modification may be involved in the development of various inflammatory responses, and whether the pathogenesis of oral ulcers is related to m6A is unclear. This study aims to identify how m6A-related single nucleotide polymorphisms (m6A-SNPs) may affect oral ulcers. The UKBB dataset containing 10,599,054 SNPs was obtained from the GWAS database using the keyword "oral ulcer" and compared with the M6AVar database containing 13,703 m6A-SNPs.With 7,490 m6A-SNPs associated with oral ulcers identified, HaploReg and RegulomeDB were used for further functional validation and differential gene analysis was performed using the GEO database dataset GSE37265. A total of 7490 m6A-SNPs were detected in this study, 11 of which were related to oral ulcers (p<5E-08), and all of these SNPs showed eQTL signals. The SNP rs11266744 (p=2.00E-27) may regulate the expression of the local gene CCRL2, thereby participating in the pathogenesis of oral ulcers. In summary, by analyzing genome-wide association studies, this study showed that m6A modification may be involved in the pathogenesis of oral ulcers and CCRL2 may be the targeted gene.

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. MATERIALS AND METHODS: 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. RESULTS: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. CONCLUSION: Signifi cant associations were found between clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.

A Novel RELA Truncating Mutation in a Familial Behçet's Disease-like Mucocutaneous Ulcerative Condition.

OBJECTIVE: Monogenic Behçet's disease (BD)-like conditions are increasingly recognized and to date have been found to predominantly involve loss-of-function variants in TNFAIP3. This study was undertaken to identify genetic and pathobiologic mechanisms associated with a BD-like mucocutaneous ulcerative syndrome and neuromyelitis optica (NMO) occurring in 3 generations of an Irish family (n = 5 cases and 5 familial controls). METHODS: Whole-exome sequencing was used to identify potential pathogenic variants in affected family members and determine segregation between affected and unaffected individuals. Relative v-rel reticuloendotheliosis viral oncogene homolog A (RELA) expression in peripheral blood mononuclear cells was compared by Western blotting. Human epithelial and RelA-/- mouse fibroblast experimental systems were used to determine the molecular impact of the RELA truncation in response to tumor necrosis factor (TNF). NF-κB signaling, transcriptional activation, apoptosis, and cytokine production were compared between wild-type and truncated RELA in experimental systems and patient samples. RESULTS: A heterozygous cytosine deletion at position c.1459 in RELA was detected in affected family members. This mutation resulted in a frameshift p.His487ThrfsTer7, producing a truncated protein disrupting 2 transactivation domains. The truncated RELA protein lacks a full transactivation domain. The RELA protein variants were expressed at equal levels in peripheral mononuclear cells. RelA-/- mouse embryonic fibroblasts (MEFs) expressing recombinant human RELAp.His487ThrfsTer7 were compared to those expressing wild-type RELA; however, there was no difference in RELA nuclear translocation. In RelA-/- MEFs, expression of RELAp.His487ThrfsTer7 resulted in a 1.98-fold higher ratio of cleaved caspase 3 to caspase 3 induced by TNF compared to wild-type RELA (P = 0.036). CONCLUSION: Our data indicate that RELA loss-of-function mutations cause BD-like autoinflammation and NMO via impaired NF-κB signaling and increased apoptosis.

IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan.

OBJECTIVES: The genetic control of Interleukin-10 (IL-10) and Tumour necrosis factor-alpha (TNF-alpha) production and the possible interaction between the two cytokines in influencing SLE susceptibility as well as clinical features has not been completely evaluated in the Taiwanese population. METHODS: We investigated the association of IL-10 and TNF-alpha promoter polymorphisms (-1082, -819 and -592 for IL-10 gene; -308 for TNF-alpha gene) with SLE in a total of 172 Taiwanese patients and 215 controls. RESULTS: Our results indicate that IL-10 A/T/A-A/T/A genotype was associated with Taiwanese SLE, whereas no significance was observed between TNF-alpha genotype and SLE. Furthermore, the TNF-alpha G allele frequency of the polymorphism at -308 was significantly decreased in patients with oral ulcers. The combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly increased in SLE patients. In addition, the combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly decreased in patients with oral ulcers. CONCLUSIONS: These results suggest a significant correlation of the combined IL-10 and TNF-alpha genetic polymorphisms contribute to SLE susceptibility and clinical features in the Taiwanese population.

Gene mapping and functional annotation of GWAS of oral ulcers using FUMA software.

Oral ulcers not only influence the physical health of patients, but they also interfere with their quality of life. However, the exact etiology of oral ulcers is not clear. To explore the roles of genetic factors in oral ulcers, a genome-wide association study of the condition in European individuals was re-evaluated by the FUMA v1.3.5e online tool. A total of 380 independent significant single nucleotide polymorphisms (SNPs) and 89 lead SNPs were identified in 34 genomic risk loci. Out of these identified genomic risk loci, 280 possible causal genes were pinpointed by positional mapping and expression quantitative trait locus mapping. Among these genes, 216 novel genes were identified. Furthermore, some genomic loci were mapped to a single gene. Functional annotation of these prioritized genes revealed that the immune response pathway was implicated in the onset of oral ulcers. Overall, our findings revealed novel possible causal genes and demonstrated that the immune response has a crucial role in the occurrence of oral ulcers.

Association of Clinical Phenotypes in Haploinsufficiency A20 (HA20) With Disrupted Domains of A20.

Background: Haploinsufficiency A20 (HA20) is a newly described monogenic disease characterized by a wide spectrum of manifestations and caused by heterozygous mutations in TNFAIP3 which encodes A20 protein. TNFAIP3 mutation leads to disruption of the A20 ovarian tumor (OTU) domain and/or the zinc finger (ZnF) domain. This study aims at exploring the association between the various manifestations of HA20 and different domains disruption of A20. Methods: We reviewed the HA20 cases in previous literature and summarized the clinical features, TNFAIP3 mutation loci and the disrupted domains caused by different sites and patterns of mutations. Patients were classified into three groups according to the A20 domains disruption. Results: A total of 89 patients from 39 families with a genetic diagnosis of HA20 were included. Overall, the age at onset of HA20 was early (median:5.92, IQR:1-10). Patients in the ZnF group showed the earliest onset (median:2.5, IQR:0.6-5), followed by patients in the OTU+ZnF group (median:6, IQR:1-10) and patients in the OTU group (median:10, IQR:8-14). The main manifestations of HA20 patients were recurrent oral ulcers (70%), recurrent fever (42%), gastrointestinal ulcers (40%), skin lesion (38%), genital ulcers (36%), and musculoskeletal disorders (34%). The percentage of patients with musculoskeletal disorders was significantly different among the three groups (p = 0.005). Patients in the OTU+ZnF group and ZnF group were more likely to develop musculoskeletal disorders than patients in the OTU group (p = 0.002 and p = 0.035, respectively). Besides, forty-three percent of HA20 patients were initially diagnosed as Behcet's disease (BD). Compared to the ZnF group, the OTU+ZnF group and OTU group had a higher percentage of patients initially diagnosed as BD (p = 0.006 and p < 0.001, respectively). Conclusion: HA20 is characterized by early-onset and the most common symptoms of HA20 are recurrent oral ulcers, fever and gastrointestinal ulcers. The onset of HA20 in patients with the ZnF domain disruption is earlier than patients with the OTU domain disruption. Compared to the OTU domain, the ZnF domain may be more closely related to musculoskeletal disorders.

Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia: CD30 analysis and clonality for T cell receptor gene re-arrangement.

INTRODUCTION: Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma OBJECTIVES: To compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative. MATERIALS AND METHODS: Retrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files. RESULTS: TUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p < 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 - 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3-9 years (mean 4.6 years) follow up. CONCLUSIONS: Analysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.

[Association between IL-10-1082G/A gene polymorphism and susceptibility of recurrent oral ulcer: meta analysis].

PURPOSE: To systematically review the association between interleukin-10 (IL-10) -1082G/A gene polymorphism and susceptibility of recurrent oral ulcer (ROU) by meta analysis. METHODS: Databases of PubMed, Embase, Web of Science, CNKI, CBM, WanFang, and VIP were electronically searched to collect studies published up to August 2017 about the association between IL-10-1082G/A gene polymorphism and ROU susceptibility. According to the inclusion and exclusion criteria, two reviewers independently screened literature and extracted data, the methodological quality assessment and heterogeneity test of included studies were performed. Meta analysis was performed with RevMan5.3 software. RESULTS: A total of 6 case-control studies were included, which involved 668 ROU patients in case group and 769 healthy individuals in control group. In the general population, the results of meta analysis showed that, under 3 genetic models including allele model (G vs A), recessive model (GG+GA vs AA) and heterozygous model (GA vs AA), there was significant association between IL-10-1082G/A gene polymorphism and ROU susceptibility (G vs A: OR=1.31, 95%CI 1.03 to 1.66, P=0.03; GG+GA vs AA: OR=1.45, 95%CI 1.16 to 1.82, P=0.001; GA vs AA: OR= 1.33, 95%CI 1.04 to 1.70, P=0.02). In the Asian population, meta analysis result was consistent with the general population. CONCLUSIONS: IL-10-1082G/A gene polymorphism is associated with ROU susceptibility. Individuals with G allele and GA genotype have a higher risk of ROU. Future more well-designed, large sample and multicenter studies are greatly needed to verify our conclusion.