Nakkuntod Jeerawat, Wongsurawat Thidathip, Charoenwongse Preeyachit, Snabboon Thiti, Sridama Vitaya, Hirankarn Nattiya
Interdepartment of Medical Microbiology, Graduate School Chulalongkorn University, Bangkok, Thailand.
Asian Pac J Allergy Immunol. 2006 Dec;24(4):207-11.
Cytokines play a key role in the regulation of immune and inflammatory responses. Therefore, cytokine genes are potentially related to susceptibility to Graves' disease (GD). The aim of this study was to investigate the putative functional polymorphisms within tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), and interleukin-1 receptor antagonist (IL-1Ra) genes, in patients with GD (n = 137) compared to a healthy Thai control group (n = 137). The results showed no statistically significant difference between the study groups for TNF-beta (Ncol site in intron 1), IFN-gamma (+874 in intron 1), and IL-1Ra (variable numbers of tandem repeats in intron 2) gene polymorphisms. Only the -863A allele within the promoter region of the TNF-alpha gene, which may affect the affinity of the promoter nuclear factor (NF)-kappab interaction, was found to be increased in GD patients compared to the controls (p = 0.009, OR = 1.8, 95% CI = 1.15 to 2.84). The effect of the -863A allele of the TNF-alpha gene was similar to the autosomal dominance mode of inheritance (p = 0.01, OR = 2, 95% CI = 1.16 to 3.44). This polymorphism may be involved in the susceptibility to GD in part through its higher promoter activity of TNF-alpha production.
细胞因子在免疫和炎症反应的调节中起关键作用。因此，细胞因子基因可能与格雷夫斯病（GD）的易感性相关。本研究旨在调查肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子-β（TNF-β）、干扰素-γ（IFN-γ）和白细胞介素-1受体拮抗剂（IL-1Ra）基因内假定的功能多态性，研究对象为137例GD患者，并与137例健康泰国对照组进行比较。结果显示，研究组在TNF-β（第1内含子中的Ncol位点）、IFN-γ（第1内含子中的+874）和IL-1Ra（第2内含子中串联重复序列的可变数目）基因多态性方面无统计学显著差异。仅发现TNF-α基因启动子区域内的-863A等位基因，其可能影响启动子核因子（NF）-κB相互作用的亲和力，与对照组相比，在GD患者中有所增加（p = 0.009，OR = 1.8，95%CI = 1.15至2.84）。TNF-α基因-863A等位基因的作用类似于常染色体显性遗传模式（p = 0.01，OR = 2，95%CI = 1.16至3.44）。这种多态性可能部分通过其较高的TNF-α产生启动子活性参与GD的易感性。
