Assessment of 14 candidate gene polymorphisms as a risk factor for oral lichen planus in Japanese population

口腔扁平苔藓（OLP）是口腔外科临床常见的一种难治性口腔黏膜疾病。虽然病因尚不清楚，但细胞介导的免疫缺陷与OLP的发病机制有关。近年来进行了大量免疫组织化学和血清免疫学研究，以确定该病的病因。最近，Carrozzo等人研究了意大利北部人群中13种细胞因子基因的遗传多态性，表明肿瘤坏死因子-α (TNF-α)和干扰素-γ (INF-γ)与OLP的疾病敏感性相关。然而，没有其他的基因研究，显示与OLP可能的遗传关联的信息很少。在本研究中，我们分析了日本OLP患者14个免疫相关基因的单核苷酸多态性（SNPs）。材料与方法：研究对象为2002年6月至2005年12月在新泻大学口腔医院口腔颌面外科门诊就诊的32例日本OLP患者和99例种族匹配的健康人。在获得知情同意后，我们采用苯酚/氯仿法从外周血中提取基因组DNA，并通过纳米入侵试验确定14个免疫相关基因的基因型，其中5个为免疫球蛋白受体基因，8个为细胞因子基因，1个为蛋白酶基因。基因型频率、等位基因频率和携带率差异的显著性采用卡方检验。结果：TNF受体2 (TNFR2)+587组患者G等位基因频率和携带率均显著高于对照组（p=0.0487、p=0.0268），优势比为2.7173（95%可信区间（CI）： 1.0995 ~ 6.7151）。免疫球蛋白G Fc受体（Fcγ r） IIIb基因与Fcγ riiib NA2等位基因频率有轻微相关性（p=0.1001），但未达到统计学意义。其他12个基因没有关联。讨论：研究表明，TNFR2（+587）基因变异调节肿瘤坏死因子α诱导的细胞凋亡，显示与系统性红斑狼疮、类风湿关节炎和严重慢性牙周炎相关。这些发现提示TNFR2（+587）基因多态性可能是与OLP易感性相关的标志物。此外，FcγRIIIb NA2等位基因频率在OLP患者中似乎有所增加。由于FcγRIIIb NA2表现出中性粒细胞功能下降，因此在更大的OLP患者群体中联合研究TNFR2（+587）和FcγIIIb基因型将是一项有趣的研究。少

Introduction : Oral lichen planus (OLP) is a refractory oral mucosal disease that is frequently encountered in the oral surgery clinic. Although the etiology is uncertain, defective cell-mediated immunity has been implicated in the pathogenesis of the OLP. In recent years, a number of immunohistochemical and serum-immunological studies have been performed for establishment of the disease etiology. Recently, Carrozzo et al. investigated genetic polymorphisms of 13 cytokine genes in the northern Italian population, indicating that tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ) were associated with disorder sensitivity of OLP. However, there has been no other genetic work, showing little information on the possible genetic association with OLP. In the present study, we analyzed the single nucleotide polymorphisms (SNPs) of 14 immune-related genes in Japanese patients with OLP.Materials and Methods : The study subjects consisted of 32 Japanese patients with OLP and 99 race-matche … More d unrelated healthy subjects referred to the Oral and Maxillofacial Surgery Clinic, Niigata University Medical and Dental Hospital between June 2002 and December 2005. After informed consent was obtained, we extracted genomic DNA from peripheral blood by the phenol/chloroform method, and determined genotypes for 14 immune-related genes, five for the immunoglobulin receptor genes, eight for cytokine genes, and one for a protease gene, with a Nano-Invader Assay. Significance of difference in the genotype frequency, allele frequency, and carriage rate was assessed by the chi-square test.Results : In TNF receptor 2 (TNFR2)+587, the G allele frequency and carriage rate were significantly higher in the patients than in the controls (p=0.0487, and p=0.0268, respectively), with an odds ratio of 2.7173 (95% confidence interval (CI) : 1.0995-6.7151). The immunoglobulin G Fc receptor (FcγR) IIIb gene was slightly associated with the frequency of the FcγRIIIb NA2 allele (p=0.1001), but failed to reach a statistical significance. There was no association for the other 12 genes.Discussion : It has been shown that the TNFR2 (+587) genetic variants regulate tumor necrosis factor-alpha-induced apoptosis, showing an asoociation with systemic lupus erythematosus, rheumatoid arthritis and severe chronic periodontitis. These findings suggested that TNFR2 (+587) genetic polymorphism would be a marker associated with susceptibility to OLP. In addition, FcγRIIIb NA2 allele frequency seemed to be increased in the OLP patients. Since FcγRIIIb NA2 exhibited a decreased neutrophil function, it would be interesting to study TNFR2 (+587) and FcγIIIb genotypes in combination in a larger group of OLP patients. Less