Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis

Abstract

Recurrent aphthous stomatitis (RAS) is a common disease with oral ulceration in which cytokines are thought to play an important role. High levels of interleukin (IL)-6, a pro-inflammatory cytokine have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if the IL-6 gene polymorphisms are associated with RAS or clinical characteristics of RAS in a cohort of Turkish population. 184 RAS patients and 150 healthy controls were included in the study. The genotypes of IL-6 gene -572G>C and -174G>C polymorphisms were determined using polymerase chain reaction based restriction fragment length polymorphism analysis. The genotype frequencies of -572G>C polymorphism showed statistically significant differences between RAS patients and controls (p = 0.01). Frequencies of GG + GC genotypes and G allele of -572G>C polymorphism were found higher in RAS patients (p = 0.0001, OR 10.8, 95 % CI 2.79-70.5; p = 0.0008, OR 2.06, 95 % CI 1.35-3.17, respectively). The genotype frequencies of -174G>C polymorphism also showed statistically significant differences between RAS patients and controls (p < 0.0001). Frequencies of GG genotype and G allele of -174G>C polymorphism were found higher in RAS patients (p < 0.0001, OR 4.87, 95 % CI 3.06-7.85; p < 0.0001, OR 3.82, 95 % CI 2.64-5.59, respectively). GG-GG combined genotype and G-G haplotype of -174G>C to -572G>C loci were also significantly higher in RAS patients (p < 0.0001 and p = 1.5 × 10(-8), respectively). After stratifying clinical and demographical characteristics of RAS patients according to IL-6 gene polymorphisms, an association was observed between family history of RAS and -174G>C polymorphism (p = 0.011). Susceptibility effects of both IL-6 gene -572G>C and -174G>C polymorphisms for RAS were observed. Further studies are necessary to prove the association of IL-6 gene polymorphisms with RAS.

Association study of interleukin‐1 family, interleukin‐6, and its receptor gene polymorphisms in patients with recurrent aphthous stomatitis

“…Our data revealed no significant differences in frequencies of alleles or genotypes of the investigated variants among healthy and RAS‐affected subjects. These findings are in disagreement with some previous studies that claimed that polymorphisms of selected cytokines were associated with an increased risk of RAS . Jing and Zhang described that IL‐1B +3954 (according to different counting +3953 as used in this study) TT genotype was significantly associated with RAS.…”

“…While Bazrafshani et al . and Karakus with colleagues reported a positive association between carriage of the IL‐6 ‐174 GG genotype and G allele and RAS, recent study by Najafi et al . found significantly higher frequency of IL‐6 ‐174 CC genotype in a group of patients with RAS.…”

“…; in other populations, only single variants were investigated. Karakus and colleagues described that the IL‐6 ‐174 and ‐572 GG haplotype were found significantly higher in RAS patients and haplotype represented by the G allele for the ‐597 and ‐174 loci appeared to favor a progressive disease in Turkey population. In contrast, our results suggest that IL‐6 haplotypes have no effect on the risk of RAS in the Czech population.…”

Recurrent Aphthous Stomatitis: Towards Evidence-Based Treatment?

“…Polymorphisms of IL-1beta and TNF-alpha production were associated with an increased risk of RAS development [15]. Genotypes of IL-6 gene -572G>C and -174G>C polymorphisms were found to be significantly higher in 184 Turkish RAS subjects [16]. Matrix metalloproteinase (MMP-9) polymorphisms have been described in RAS patients [17], and a mutation of methylene tetrahydrofolate reductase (MTHFR) gene C677T related slightly curiously with the number of oral ulcers in RAS patients [18].…”

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis

“…Patients with RAS were diagnosed and examined based on accepted clinical criteria by medicine specialists from the Department of Immunology and Microbiology, General University Hospital and First Faculty of Medicine, Charles University, Prague, and from the Department of Clinical Immunology and Allergology, Institution Shared with St. Anne's Faculty Hospital, Faculty of Medicine, Masaryk University. RAS was classified into three clinical subtypes, according to Karakus et al: (a) major (larger than 1 cm in diameter and deeper than the minor form; healing within 10‐30 days); (b) minor (<1 cm in diameter; healing within 10‐14 days); and (c) herpetiform aphthae (grouped aphthae, 1‐2 mm in size).…”