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.

Therapeutic and Analgesic Efficacy of Laser in Conjunction With Pharmaceutical Therapy for Trigeminal Neuralgia.

Introduction: Trigeminal neuralgia (TN) is the most common neuralgia in the head and neck region and a common cause of orofacial pain. It is routinely treated with carbamazepine. Laser, acupuncture and radiofrequency are among other treatment modalities for this condition. This study sought to assess the efficacy of laser therapy in conjunction with carbamazepine for treatment of TN. Methods: A total of 30 patients who met the inclusion criteria were divided into 2 groups of cases and controls (n=15) by double blind randomized controlled clinical trial. All patients received 100 mg carbamazepine at baseline and another 100 mg after 2 days for pain control. In the case group, low level laser therapy (LLLT) was also performed in addition to pharmaceutical therapy. Sham laser was used in the control group instead of LLLT. Treatment was continued for 9 sessions (3 days a week). The intensity of pain was measured and compared in the 2 groups using visual analog scale (VAS) in 3 period. The qualitative variables among the groups were compared using the repeated measures analysis of variance (ANOVA). Results: The severity of pain was lower at the end of treatment in the case compared to the control group so this difference was statistically significant (P=0.003). The severity of pain decreased in both groups over time. Significant difference was noted in this regard between the 2 groups either (P=0.003). At the end of treatment pain intensity dropped in the intervention group from 6/8 to 1/2 and control group from 6/6 to 2/7. Conclusion: Laser therapy did add to the value of pharmaceutical therapy for treatment of TN. Both groups experienced significant improvement over time. So it is better to used laser complementary therapy to reduce side effects and the medicine dosage.

Autosomal dominant deficiency of the interleukin-17F in recurrent aphthous stomatitis: Possible novel mutation in a new entity.

Recurrent Aphthous Stomatitis (RAS) is a common oral inflammatory disease with unknown pathogenesis. Although the immune system alterations could be involved in predisposition of individuals to oral candidiasis, precise etiologies of RAS have not been understood yet. A recent study showed that autosomal dominant IL17F deficiency could cause chronic mucocutaneous candidiasis. Considering the inflammatory nature of interleukin (IL)-17F and RAS, this study was performed to check any disease-associated mutation in a number of patients with RAS. Sixty-two Iranian individuals with RAS were investigated in this study. After DNA extraction using a phenol-chloroform method from the whole blood, amplification was accomplished by polymerase chain reaction and the products were sequenced using a 3730 ABI sequencer. The results of sequencing revealed a missense, heterozygous mutation of IL17F, converting a threonine to proline in a patient with RAS (T79P). The Poly-phen software suggested a damaging probability predicting this substitution to have a harmful effect on IL-17F protein function. This mutation was checked in fifty healthy individuals, and was not detected in any of them. This is the first study showing that a mutation in IL-17F is associated with susceptibility to RAS. However, functional studies and further studies on more patients with RAS are required to confirm such association.

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.

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.

HLA-DRB and HLA-DQB Allele and Haplotype Frequencies in Iranian Patients with Recurrent Aphthous Stomatitis.

Recurrent aphthous stomatitis (RAS) is known as the most common chronic disease of the oral cavity, which affects a range of 5-25% of the population. RAS appears to be associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. This study attempts to survey the distribution of HLA-DRB and -DQB alleles among Iranian RAS patients and healthy controls. In order to evaluate the association of HLA-DR and DQ alleles and haplotypes, 54 patients with RAS and 100 unrelated healthy subjects as control group were investigated. Our data indicated that DRB1*13:17, DRB1*15:01, and DRB5*01 were significantly more frequent in RAS patients in comparison to controls. However, DRB3:01allele frequency was higher in the controls compared to the patients. The significantly frequent allele in the patients compared with the healthy subjects was HLA-DQB1*03:02. However, both HLA-DQB1*02:01 and HLA-DQB1*03:01 alleles were most frequent in the healthy individuals rather than the patients. The DRB*04/DQB1*03:01 and DRB*01:01/DQB1*02:01 haplotypes were significantly distributed in healthy subjects compared with patients. However, DRB*07:01/DQB1*03:02 haplotype was found to be significantly frequent in patients than controls. In respect of HLA genes, factors are involved in the incidence of RAS; various HLA-DRB and HLA-DQB1 alleles and the related haplotypes are suggested to be the three main RAS susceptibility factors in our population study.

Evaluation of antioxidant efficacy of Purslane extract in Patients with Recurrent Aphthous Stomatitis: a randomized, placebo-controlled, triple-blinded, clinical trial

Background: This herbal medicine is considered a rich source of antioxidants with anti-inflammatory effects. The purpose of this study was to evaluate the effectiveness of purslane in treatment of recurrent aphthous stomatitis (RAS) and also it ̓s effect on antioxidant level. Materials and methods: 50 patients were selected for this randomized triple-blind placebo-controlled trial. All subjects were randomly divided in to two groups, one group received purslane (n=25) and another group, placebo (n=25) for 3 month. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and total antioxidant status (TAS) was measured in plasma at baseline and after 3 month of treatment. Also pain intensity based on the visual analogue scale (VAS), the mean interval between lesion, number of lesions and the mean duration of complete healing at baseline and in month 1, 2 and 3 were recorded. Statistical analysis was performed by using Mann-Whitney and T-test. Results: A significant decrease in pain intensity in VAS scores was seen after treatment in intervention group (p<0.001). The mean duration of complete healing showed significant differences (P<0.001) between the two groups. The mean interval between lesions also showed significant differences (P<0.001) among the intervention group (33.12 days) compared with the placebo group (17.88 days). No significant differences were found regarding the number of lesions, level of erythrocyte GSHPx, TAS and SOD. No serious side-effects occurred in either of groups. Conclusions: According to this study, purslane is clinically effective in treatment of RAS (number of lesions, pain intensity and duration of healing) although it is unable to change the level of antioxidants. (AU)

NLRP3 gene polymorphisms in Iranian patients with recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common disorder with an unclear etiopathogenesis. Involvement of the immune system in the development of this condition is strongly suggested. As the variations in the inflammasome-related NLRP3 gene have been suggested to affect immune system activity, this case-control study was performed to determine whether these genetic variants are associated with RAS. METHODS: We studied a group of 69 Iranian patients with RAS in comparison with 56 healthy controls. We determined four single nucleotide polymorphisms (SNPs) of NLRP3 and performed association analyses of NLRP3. Genotyping was conducted using the TaqMan method. RESULTS: The NLRP3 rs3806265 T allele was significantly more frequent in the patients with RAS than in the healthy controls (P = 0.003). While a significant negative association was found between the C allele at the same position with RAS (P = 0.003), the TT genotype was significantly more frequent at position rs3806265 in NLRP3 in patient group than in the controls (P = 0.002). However, the frequency of CT genotype at the same position was significantly higher in healthy controls than in the case category (P = 0.002). CONCLUSIONS: Considering the high frequency of the presence of NLRP3 rs3806265 TT genotype in patients with RAS, it seems that this gene polymorphism could affect individual susceptibility to RAS.

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.