Oral Lichen Planus Susceptibility Research Articles

Evaluation of the association between TNF-α-1031 T/C polymorphism with oral lichen planus disease

BackgroundOral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population.MethodSaliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software.ResultsThe findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity.ConclusionsThese findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease.

Association of polymorphisms in Th1/Th2-related cytokines (IFN-γ, TGFβ1, IL-1β, IL-2, IL-4, IL-18) with oral lichen planus: A pooled analysis of case–control studies

Background/purposeIncreasing evidence suggests that single-nucleotide polymorphisms (SNPs) in Th1/Th2-related cytokine genes correlated with oral lichen planus (OLP) susceptibility. However, these results were inconsistent and inconclusive. Hence, the aim of this study is to draw a more precise estimation of the genetic associations between SNPs in 6 cytokines (IFN-γ, IL-18, TGFβ1, IL-1β, IL-2, IL-4) and OLP. Materials and methodsA systematic literature search was conducted to identify all eligible case–control studies on the association between SNPs in 6 cytokines and OLP susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. ResultsA significant association of IFN-γ (874A/T) polymorphism with OLP was found (OR, 1.49; 95%CI, 1.22–1.81; P < 0.001) based on 6 eligible studies. A significant association of IL-18 (137G/C) polymorphism with OLP was found (OR, 1.64; 95%CI, 1.24–2.18; P < 0.001) based on 3 studies. A marginally significant association of TGFβ1 (509C/T) polymorphism in allele model with OLP was found (OR, 1.31; 95%CI, 1.01–1.71; P = 0.05) based on 4 studies. Nevertheless, lack of significant association of IL-1β (3954C/T), IL-2 (330T/G), IL-4 (590C/T), and IL-18 (607C/A) polymorphisms with OLP was found (P > 0.05) based on 3 studies, respectively. ConclusionThis is the first meta-analysis to investigate the associations of 6 cytokines polymorphisms with OLP, suggesting that SNPs in IFN-γ, IL-18, and TGFβ1 may act as genetic factors for OLP risk. Further well-designed studies with larger sample size and multiple ethnicities are needed to validate these associations.

Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population

BackgroundVitamin D receptor (VDR) is involved in multiple immune-mediated disorders including oral lichen planus (OLP). This study investigated the association between VDR gene polymorphisms and the risk of OLP.MethodsIn total, 177 OLP patients and 207 healthy participants were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Eight single nucleotide polymorphisms (SNPs: rs731236, rs739837, rs757343, rs2107301, rs2239185, rs7975232, rs11574129 and rs11568820) in the VDR gene were selected and genotyped.ResultsThe results showed that OLP risk was increased in subjects with the rs2239185 TT genotype (Recessive model: adjusted Odd ratio(OR) = 2.68, 95% Confidence interval(CI) = 1.28–5.62, P = 0.009) and rs7975232 CC genotype (Recessive model: adjusted OR = 2.25, 95% CI = 1.10–4.58, P = 0.026). Moreover, rs2239185 and rs7975232 (P < 0.01) showed significant cumulative effects on OLP risk.Haplotype analysis showed that the CC haplotype (rs2239185-rs7975232) was associated with an increased risk of OLP (OR = 3.11, 95% CI = 1.42–6.83, P = 0.005), compared with the AC haplotype.Conclusion: The rs2239185 and rs7975232 variants of VDR may influence OLP susceptibility, and VDR gene polymorphisms may be candidate susceptibility regions for OLP in a Chinese Han population.

Association of Interferon-gamma Gene Polymorphism (+874 A/T) and Oral Lichen planus susceptibility: Systematic Review and Meta-Analysis

Association of Interferon-gamma Gene Polymorphism (+874 A/T) and Oral Lichen planus susceptibility: Systematic Review and Meta-Analysis

Mannose-Binding Lectin 2 (MBL2) combined genotypes deficiency is associated with susceptibility for Oral Lichen Planus.

Oral Lichen Planus (OLP) is an oral inflammatory condition, mediated by host immune system reaction, presenting basal membrane damages with inflammatory lesions in the mouth and/or skin. In this study, the role of functional polymorphisms in the MBL2 gene, encoding for Mannose-Binding Protein C (MBP-C), a member of the innate immune response and an acute-phase protein able to activate the complement cascade, was investigated to assess a possible association with OLP susceptibility in Italian patients. Two variations at the promoter region (called H/L and X/Y) and three at the first exon (at codon 52, 54, and 57) of the MBL2 gene were analyzed in 69 OLP patients and 244 healthy controls from northeastern Italy. Considering the polymorphisms singularly, the MBL2 X allele and C/T genotype of the D allele (correlated with low MBP-C expression) were associated with susceptibility to develop OLP. Moreover, when taking into account MBL2 combined genotypes, more OLP patients were deficient MBP-C producers than not deficient, who were more represented among healthy controls. MBL2 combined genotypes, responsible for deficient MBP-C production, are associated with an increased risk of developing OLP.

Association between polymorphisms in interleukins and oral lichen planus: A meta-analysis.

More and more studies have suggested that single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes are correlated with an increased risk of developing oral lichen planus (OLP). However, these results were inconsistent. Therefore, the aim of this meta-analysis is to retrieve and comprehensively analyze all related clinical studies to investigate the association of ILs gene polymorphisms with the OLP risk. PubMed, Embase, and the Cochrane Library were searched for eligible studies to evaluate the association between IL polymorphisms and the OLP. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Statistical analyses were performed by using STATA software. In all 6 studies, including 4 SNPs (IL6-174G/C, IL10-592C/A, IL10-819C/T, and IL10-1082G/A), 362 OLP patients and 622 non-OLP control subjects from five different countries were investigated. As for the IL6-174G/C, IL10-819C/T, and IL10-1082G/A, no evidence was found to support the association between SNP and OLP susceptibility in any genetic models. However, as for IL10-592C/A, a significant relationship between them was identified in all of comparison models (C vs A: OR = 0.724, 95% CI = 0.585-0.897, P = 0.003; CC vs AA: OR = 0.447, 95% CI = 0.276-0.722, P = 0.001; AC vs AA: OR = 0.585, 95% CI = 0.387-0.883, P = 0.011; CC+AC vs AA: OR = 0.544, 95% CI = 0.365-0.809, P = 0.003; CC vs AA+AC: OR = 0.715, 95% CI = 0.515-0.994, P = 0.046). With the presently available evidence, this meta-analysis fails to show the statistical associations between IL6-174G/C, IL10-819C/T, and IL10-1082G/A and OLP susceptibility in any genetic models. However, the A allele and AA genotype in IL10-592C/A polymorphism may increase the risk of OLP. In the future, more well-designed studies with larger sample sizes are needed.

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-β1 gene with oral lichen planus susceptibility.

BackgroundOral lichen planus (OLP) is a premalignant mucocutaneous disease in which genetic factors and immune responses play a major role. Cytokines play an important role in the pathogenesis and disease progression of OLP. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1 on OLP susceptibility in a Saudi cohort.MethodsForty two unrelated patients with OLP and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms.ResultsThe frequency of genotype AT of IFN-γ (874A/T) was significantly higher while genotype AA was lower in OLP patients as compared to controls (P < 0.05). The frequency of T containing genotypes (AT + TT) was also higher in OLP patients as compared to that in controls (P = 0.003). The frequencies of allele T was higher while that of allele A lower in patients than the controls however the difference was not statistically significant (P = 0.07). There was no significant difference in the frequencies of alleles and genotypes of IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms between patient and control groups. These results indicated that genotype AT of IFN-γ (874A/T) polymorphism is associated with OLP risk and genotype AA is protective to OLP. On the other hand the polymorphisms IL-6 (174G/C) and TGF-β1 (509C/T) may not be associated with OLP risk in our population.ConclusionIt is concluded that IFN-γ (874A/T) polymorphism is associated with the susceptibility of OLP, however further studies with large sample size involving different ethnic populations should be conducted to strengthen our results.

Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment.

Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk.

The current study investigated the association between VDR EcoRV (rs4516035), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), CYP27B1 (rs4646536), CYP24A1 (rs2296241), and MTHFR (rs1801133) gene polymorphisms and risk of oral lichen planus (OLP) occurrence. The study group consisted of 65 oral lichen planus patients and 100 healthy blood donors in the control group. Single nucleotide polymorphisms were genotyped by real time PCR or PCR-restriction fragment length polymorphism (RFLP) method. Heterozygous as well as mutated genotype of vitamin D receptor (VDR) FokI (rs2228570) polymorphism was associated with increased oral lichen planus risk in comparison with wild type genotype (odds ratio (OR) = 3.877, p = 0.017, OR = 38.153, p = 0.001, respectively). A significantly decreased OLP risk was observed for heterozygous genotype of rs2296241 polymorphism in CYP24A1 gene compared with the wild type form (OR = 0.314, p = 0.012). VDR gene polymorphisms ApaI and TaqI were in linkage disequilibrium (D' = 0.71, r(2) = 0.22). Identified haplotype AT was associated with decreased OLP risk (OR = 0.592, p = 0.047). Our results highlight the possible important role of VDR FokI (rs2228570) and CYP24A1 rs2296241 gene polymorphisms for oral lichen planus susceptibility. Identification of new molecular biomarkers could potentially contribute to determination of individuals with OLP predisposition.

Association of CD24 and the adenomatous polyposis coli gene polymorphisms with oral lichen planus

CD24 and the adenomatous polyposis coli (APC) gene polymorphisms are known to predispose to malignant disease. We aimed to investigate their association with risk and susceptibility of oral lichen planus (OLP) in an Israeli Jewish population. The study included 54 patients, of which 41 were females (75.9%) and 13 males (24.1%); of the 533 controls, 224 were females (42.0%) and 309 males (57.9%). Genotyping was performed. Two APC (I1307 K, E1317 Q) and four CD24 variants--C170 T (rs52812045), TG1527 del (rs3838646), A1626 G (rs1058881), and A1056 G (rs1058818)--were assessed. Frequencies were analyzed using the Chi-square test. Two-sided P < .05 values were considered significant. Odds ratios and 95% confidence intervals were obtained by logistic regression analyses. CD24 A1056 G carriers have a significantly lower risk of OLP compared with individuals with the wild-type variant (P = .001). A significantly lower risk was found for heterozygote (P = .008) and homozygote carriers (P = .002). Homozygote CD24 A1626 G carriers had a significant higher risk for OLP compared with nonhomozygote carriers (P = .040). CD24 C170 T, TG1527 del, and APC polymorphisms did not show significant associations with OLP risk. CD24 A1626 G is more frequent in OLP patients, contributes to disease risk, and could play a role in OLP susceptibility. A significant association between CD24 A1056 G and a lower OLP incidence was found, suggesting that it may confer protection against OLP risk and progression.

Association of interleukin 12A gene polymorphisms with oral lichen planus in Chinese population.

Oral lichen planus (OLP) is a common autoimmune disorder with genetic and environmental factors contributing to its etiology. Interleukin (IL) 12 is a pro-inflammatory cytokine, which favors the differentiation of T helper 1 (Th1) cells, and forms a link between innate resistance and adaptive immunity. This study aimed to investigate the association between OLP susceptibility and clinical type in Chinese Han population with single-nucleotide polymorphisms (SNPs) of IL-12A gene. Five SNPs of the IL-12A gene at positions rs2243115, rs2243123, rs583911, rs568408, and rs2243143 were performed in 292 patients with OLP and 686 healthy controls from East China. The five SNPs were genotyped by TaqMan PCR method. The genotype and allelic frequencies were calculated and analyzed. There was a significant difference in rs568408 genotype distributions between patients and controls (P = 0.043). Additionally, there were highly significant increases in rs568408 genotype distributions and allele A frequencies in the erosive OLP group as compared to the control group (P = 0.011, OR = 1.76, 95% CI: 1.133 -2.732). Our study indicated that the rs568408 variation in IL-12A gene could influence disease susceptibility, and was associated with the severity of OLP in our East Chinese cohort.

Inflammation‐related cytokines in oral lichen planus: an overview

Cytokines are powerful mediators which play a central role in both innate and adapted immune responses. Aberrant productions of cytokines may lead to the onset of immune deficiency, allergy or autoimmunity, which are involved in the mechanisms of various immune-mediated inflammatory diseases. Oral lichen planus (OLP) is a chronic inflammation disease affecting the oral mucosa with unknown aetiology. Previous studies have described the abnormal expression patterns of various inflammation-related cytokines, such as IL-1, 2, 4, 5, 6, 8, 10, 12, 17, 18, TGF-β, IFN-γ and TNF-α, in lesions, saliva, serum and peripheral blood mononuclear cells from patients with OLP, which may reflect the immune dysregulation status and emerge as central players in the immunopathogenesis of OLP. Besides, the gene polymorphisms of several cytokines such as IFN-γ, TNF-α, IL-4, IL-10 have been found to be involved in the susceptibility of OLP. In this review, we gave a brief introduction of the characteristics and biological functions of these inflammation-related cytokines and summarized for the first time the current knowledge on the involvement of inflammation-related cytokines in OLP. Further research on the exact roles of these cytokines will aid the understanding of the pathogenesis and the identification of novel therapeutic approaches of OLP.

Mitochondrial haplogroup B4 may be a protective factor to oral lichen planus susceptibility in Chinese

Oral lichen planus (OLP) is a common inflammatory disorder with a higher prevalence among women than men. The pathogenesis of OLP is still unclear, and its heredity is not well characterized. Maternal inheritance of mitochondrial DNA (mtDNA) indicates its importance in human ethnic group classification as well disease susceptibility. So, this study was conducted to find whether mtDNA haplogroup associates with OLP susceptibility in Chinese, and determine the influence of C-stretch structure of mtDNA on OLP susceptibility. We sequenced three hypervariable regions of mtDNA from 242 patients with OLP and 237 healthy controls. The association between mtDNA haplogroups and OLP is tested by chi-square test. Seventeen kinds of haplogroups were identified, and the frequency of haplogroup B4 was significantly higher in control group than that of the OLP group (P = 0.013, OR=0.429). In female samples, B4 declared even more significance (P = 0.003, OR=0.296). Meanwhile, the haplotypes of C-stretch in mtDNA did not have any significant difference between case-control groups. Mitochondrial DNA haplogroup B4 might have a protective effect to OLP, and its protective effect resides predominantly in women. However, the association between C-stretch haplotype and OLP susceptibility still needs more patients for evaluation.

The pathogenesis of oral lichen planus.

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.