Choi J H, Kim S H, Cho B Y, Lee S K, Kim S H, Suh C H, Park H S
Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea.
J Clin Pharm Ther. 2009 Apr;34(2):231-8. doi: 10.1111/j.1365-2710.2008.00979.x.
Although the pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-alpha, a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-alpha promoter polymorphisms in the development of AIU, we performed an association study of TNF-alpha promoter polymorphisms with AIU phenotype.
Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-alpha gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a single-base extension method. Haplotype analyses were done.
The genotype frequencies of TNF-1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controls in both co-dominant (P = 0.014, P = 0.007) and dominant (P = 0.007, P = 0.004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P = 0.004, Pc = 0.02) and dominant models (P = 0.002, Pc = 0.01).
These findings suggest that the two promoter polymorphisms of TNF-alpha at -1031T>C and -863C>A may contribute to the development of AIU.
尽管阿司匹林诱导的荨麻疹（AIU）的发病机制尚未完全明确，但已注意到AIU患者存在肥大细胞活化现象。肿瘤坏死因子（TNF）-α是一种强效促炎细胞因子，在荨麻疹患者中，人皮肤肥大细胞和其他炎症细胞可释放该因子。为研究TNF-α启动子多态性在AIU发病中的作用，我们进行了TNF-α启动子多态性与AIU表型的关联研究。
纳入239例AIU患者，其中包括120例阿司匹林不耐受慢性荨麻疹（AICU）患者和119例阿司匹林不耐受急性荨麻疹（AIAU）患者，以及524名正常对照者。通过口服阿司匹林激发试验确诊AIU。采用单碱基延伸法对TNF-α基因中的5个单核苷酸多态性（SNPs）（-1031T>C、-863C>A、-857C>T、-308G>A、-238G>A）进行基因分型，并进行单倍型分析。
在共显性（P = 0.014，P = 0.007）和显性（P = 0.007，P = 0.004）模型中，AIU患者中TNF-1031T>C和TNF-863C>A的基因型频率均显著高于正常对照者。在共显性（P = 0.004，Pc = 0.02）和显性模型（P = 0.002，Pc = 0.01）中，AIU组中含有TNF-ht2[CACGG]基因型的频率均显著高于正常对照者。
这些发现提示，TNF-α基因-1031T>C和-863C>A这两个启动子多态性可能与AIU的发病有关。
