Bernstein Joel M, Anon Jack B, Rontal Michael, Conroy Jeffrey, Wang Chong, Sucheston Lara
Department of Otolaryngology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Laryngoscope. 2009 Jul;119(7):1258-64. doi: 10.1002/lary.20239.
OBJECTIVES/HYPOTHESIS: Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP).
Case control study.
Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression.
The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups.
TNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.
目的/假设：尽管在鼻息肉组织中已鉴定出许多促炎细胞因子，但导致这种以水肿、淋巴细胞增多和嗜酸性粒细胞增多为特征的炎症的初始触发因素仍不清楚。本研究的目的是确定促炎、抗炎和趋化因子基因中可能导致慢性增生性鼻窦炎伴鼻息肉（CHSwNP）遗传易感性的基因多态性的存在情况。
病例对照研究。
采用Purgene DNA纯化方案（Gentra）从179例CHSwNP患者和153例无息肉对照的左右口腔黏膜表面采集颊拭子。使用iPlex Gold和Mass Array Compact系统（Sequenom，圣地亚哥，加利福尼亚）对14种细胞因子基因进行细胞因子基因座的基因分型检测。在病例组和对照组中分别进行Hardy-Weinberg平衡比例检验。使用无条件逻辑回归对每个单核苷酸多态性（SNP）的等位基因与病例对照状态之间的关联证据进行检验。
位于肿瘤坏死因子（TNF）-α（rs1800629）中的一个SNP的A等位基因频率在鼻息肉患者与无鼻息肉对照中存在显著差异，分别为18.6%和11.5%，在该SNP至少有一个A等位基因拷贝的情况下，个体患鼻息肉的易感性几率增加近两倍（优势比，1.86；置信区间，1.4 - 3.09）。两组之间所有其他炎症、抗炎和趋化因子基因的细胞因子基因多态性在统计学上无差异。
TNF-α - 308，该细胞因子基因启动子区域的一个SNP与鼻息肉发病几率增加有关。TNF-α是一种强效免疫介质和促炎细胞因子，已被认为与大量人类疾病的发病机制有关。该基因位于6号染色体短臂上，与主要组织相容性复合体基因和补体在一起，增加了该基因座内的多态性可能导致该基因组区域与多种感染性和自身免疫性疾病存在遗传关联的可能性。
