Tumor Necrosis Factor-α and Interferon-γ Polymorphisms Contribute to Susceptibility to Oral Lichen Planus

Abstract

Most lymphocytes in the lamina propria of oral lichen planus (OLP) lesions express and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), whereas they do not secret interleukin-4 and -10 or transforming growth factor-beta. We analyzed whether the polymorphisms of several cytokines may influence the susceptibility to OLP. Cytokine typing was performed by a sequence-specific PCR assay. Thirteen cytokine genes with 22 single-nucleotide polymorphisms were studied. IFN-gamma UTR 5644 genotype frequencies showed a significant increase in number of T/T homozygotes in OLP patients compared with controls (40.9 vs. 22.9%; p=0.0022). Moreover, in OLP patients, the frequency of the -308A TNF-alpha allele was higher than in the controls (21.6 vs. 9.3%; p < 0.05) causing a significantly increased frequency of the genotype G/A in OLP (43.2 vs. 14.3%; p=0.0002). Because in patients with mucocutaneous lichen planus (LP), the frequency of the -308A TNF-alpha allele was more than double the values in the pure OLP patients (40.9 vs. 15.1%; p=0.003), the -308G/A TNF-alpha genotype showed a significantly higher frequency in patients with mucocutaneous LP than in patients with pure OLP (81.8 vs. 30.3%, p=0.003). In conclusion, we suggest that genetic polymorphism of the first intron of the promoter gene of IFN-gamma may be an important risk factor to develop oral lesions of LP, whereas an increase in the frequency of -308A TNF-alpha allele may best contribute to the development of additional skin involvement.

Possible Role of TNF-α, IFN-γ, FAS/APO1 in the Etiopathogenesis of Lichen Planus

“…Carrozzo et al investigated the polymorphism of IFN-γ and TNF-α using polymerase chain reaction (PCR) in 44 cases with LP and reported that these cytokines influence the clinical type of the disease and contribute to the predisposition to LP, and they stressed that their results contradicted those of previous studies [30]. Yamamoto et al evaluated the serum IFN-γ levels of 30 patients diagnosed with OLP by enzyme immunoassay method and found serum IFN-γ production to be slightly lower than in the control group.…”

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

“…Indeed, cutaneous idiopathic LP is frequently associated with the HLA-DR1 allele, whereas idiopathic OLP is not [9]. However, a linkage disequilibrium of the -308A TNF-α promoter polymorphism with HLA-DR3 has reported in Caucasians [10]. Recently, the gene for cytotoxic T lymphocyte antigen 4 (CTLA-4) has been identified, able to confer the susceptibility to HT [6].…”

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

“…The significantly increased frequencies of the UTR 5644T allele and AT and TT genotypes in our GO patients are in support of the hypothesis. This polymorphism is involved in pathogenesis of Behcet's disease 36 and lichen planus, 37 but to our knowledge this study is the first to suggest the involvement of this polymorphism in GO.…”