Relationship between nuclear factor-κB signaling pathway and susceptibility of recurrent aphthous ulcer

doi:10.19439/j.sjos.2018.05.014

Abstract

Abstract: PURPOSE: To explore the possible relationship between recurrent aphthous ulcer (RAU) and nuclear factor-κB signaling pathway. METHODS: A total of 124 RAU patients were recruited for this study. The control group consisted of 133 healthy subjects. Serum NFκBp50, NFκBp65, IκBα and IKK concentration were detected by ELISA.NFκB-94 ins/del ATTG sites were detected by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Relative risk ratios were estimated by odds ratios (OR) and 95% confidence interval (95%CI). Statistical analysis was performed using SPSS 20.0 software package. RESULTS: Serum NFκBp50, NFκBp65 and IKK levels in RAU patients were significantly lower than those of the controls (P<0.05). Serum IκBα level in RAU patients was significantly higher than those of the controls (P<0.05). Significant differences were found in the genotype frequencies or allele frequencies of NFκB-94 ins/del ATTG sites between RAU patients and controls (P<0.05). ID genotype（OR=3.073,95%CI=1.557-6.067）, DD genotype (OR=4.851,95%CI=2.264-10.393), and D allele （OR=2.079,95%CI=1.462-2.957） at NFκB-94 ins/del ATTG site exhibited high risks of RAU. CONCLUSIONS: NF kappa B signaling pathway is associated with RAU.NFκB-94 ins/del ATTG sites are associated with higher risk of RAU. NFκB-94 ins/del ATTG D allele may serve as genetic determinants for RAU.

Key words: Nuclear factor-κB -94 ins/del ATTG, Recurrent aphthous ulcer, Signaling pathway, Gene polymorphism

CLC Number:

R781.5

ZHANG Jing, LINGHU Rui-qi, SHA Jing-jing, HU Xin-pei, LI Dan, LI Meng-yuan. Relationship between nuclear factor-κB signaling pathway and susceptibility of recurrent aphthous ulcer[J]. Shanghai Journal of Stomatology, 2018, 27(5): 513-517.

References

[1] 陈谦明. 口腔黏膜病学 [M]. 第4版. 北京: 人民卫生出版社, 2012: 64.
[2] Avci E, Akarslan ZZ, Erten H, et al.Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers[J]. Braz J Med Biol Res, 2014, 47(5): 355-360.
[3] 邹玉红, 杨静, 陈春华. 复发性口腔溃疡患者血清中TNF-α、IL-2,6与免疫功能的相关性[J]. 海南医学院学报, 2015, 21(9): 1299-1301.
[4] 张敬, 王婷婷, 漆明. 复发性阿弗他溃疡患者外周血中TGF-β1和IL-10 的表达水平及其临床意义[J].实用口腔医学杂志, 2014, 30(1): 82-84.
[5] 张敬, 沙晶晶, 龚娟. 转化生长因子β1和白细胞介素10单核苷酸多态性与复发性口腔溃疡易感性的研究[J]. 华西口腔医学杂志, 2016, 34(1): 27-31.
[6] 张敬, 沙晶晶, 龚娟. IFN-γ+874A/T位点和IL-2 -330T/G位点的单核苷酸多态性与复发性口腔溃疡易感性的关系[J]. 实用口腔医学杂志, 2016, 32(6): 852-856.
[7] Bank S, Andersen PS, Burisch J, et al.Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFκBIA, NFκB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort[J]. PLoS One, 2014, 9(6): e98815.
[8] Fan Y, Mao R, Yang J.NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer[J]. Protein Cell, 2013, 4(3): 176-185.
[9] Ballard DW, Walker WH, Doerre S, et al.The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-κB function[J]. Cell 1990, 63(4): 803-814.
[10] Yin JY, Wang HW, Ulla V, et al.Association and interaction of NFΚB1 rs28362491 insertion/deletion ATTG polymorphism and PPP1R13L and CD3EAP related to lung cancer risk in a Chinese population[J]. Tumor Biol, 2016, 37(4): 5467-5473.
[11] 赖红梅. NFΚBIA、NFΚB1基因多态性与冠心病及血浆IL-6水平相关性研究 [D]. 乌鲁木齐: 新疆医科大学, 2015.
[12] Akintoye SO, Greenberg MS.Recurrent aphthous stomatitis[J]. Dent Clin North Am, 2014, 58(2): 281-297.
[13] 刘好好, 许子悦, 谢春雨, 等. 复发性口腔溃疡与T细胞免疫研究进展[J].现代免疫学, 2016, 36(1): 72-75.
[14] 张琪. NF-κB信号通路基因多态性与乙肝病毒在乙肝相关肝病发生中的作用研究[D].上海: 第二军医大学, 2014.
[15] Elinav E, Nowarski R, Thaiss CA, et al.Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms[J]. Nat Rev Cancer, 2013, 13(11): 759-771.
[16] Charbonneau B, Block MS, Bamlet WR, et al.Risk of ovarian cancer and the NF-κappaB pathway: genetic association with IL1A and TNFSF10[J]. Cancer RES, 2014, 74(3): 852-861.
[17] 李亚然, 于敏, 莫炜. NF-κB信号通路与血管间黏附分子间作用及其在疾病治疗中的应用[J]. 药物生物技术, 2017, 24(1): 58-62.
[18] 时美静, 李睿岩, 张玉彬. 中药治疗溃疡性结肠炎所涉信号通路研究进展[J].药学进展, 2016, 40(8): 610-618.
[19] 王鹏程, 赵珊, 冯健, 等. 基于NF-κB信号通路的中药抗溃疡性结肠炎研究进展[J].中草药, 2015, 46(10): 1556-1561.
[20] 范亚欣, 于卫健, 梁晓华, 等. 辽宁汉族人群NFκB1基因启动子区域-94 ins /del ATTG多态性研究[J]. 中国输血杂志, 2012, 25(4): 333-335.
[21] 雷媛, 邓长生. NFκB1基因启动子区域多态性与中国湖北汉族人溃疡性结肠炎的关系[J]. 世界华人消化杂志, 2009, 17(21): 2212-2216.
[22] 商晶晶. NF-κB和PXR基因多态性与中国汉族人群风湿性心脏病易感性的关系 [D].长沙: 中南大学, 2013.
[23] 岑晗. NF-κB信号通路相关基因多态性及其交互作用与系统性红斑狼疮的关联性研究[D]. 合肥: 安徽医科大学, 2014.
[24] Mohd Suzairi MS, Tan SC, Ahmad Aizat AA, et al.The functional -94 insertion/deletion ATTG polymorphism in the promoter region of NFΚB1 gene increases the risk of sporadic colorectal cancer[J]. Cancer Epidemiol, 2013, 37(5): 634-638.
[25] 郭俊宇, 韦叶生, 周喜汉, 等. 广西汉族和壮族人群NFκB1基因多态性[J].中国现代医学杂志, 2010, 20(14): 2142-2145.