Chang Y T, Liu H N, Yu C W, Lin M W, Huang C H, Chen C C, Liu M T, Lee D D, Wang W J, Tsai S F
Department of Dermatology, Taipei Veterans General Hospital, Shih-Pai, Taipei 11217, Taiwan, Republic of China.
Br J Dermatol. 2006 Jan;154(1):79-84. doi: 10.1111/j.1365-2133.2005.06938.x.
Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP.
We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP.
DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes.
Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed.
The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.
大疱性类天疱疮（BP）是一种自身免疫性大疱性疾病，主要与针对半桥粒BP自身抗原BP180和BP230的自身抗体相关。在BP患者的皮肤病变或血清中已检测到高水平的白细胞介素（IL）-1β、IL-4、IL-5、IL-6、IL-8、IL-10、IL-13、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ。细胞因子基因多态性可能影响细胞因子的产生，并导致自身免疫性疾病易感性增加。迄今为止，尚未对BP患者进行细胞因子基因多态性研究。
我们旨在确定细胞因子基因的遗传多态性是否可能影响BP的发生发展。
从96例BP患者和174例对照受试者中获取DNA样本。使用直接测序和微卫星基因分型，我们检测了11个细胞因子基因中的23个多态性，包括IL-1α、IL-1β、IL-1受体拮抗剂、IL-4、IL-6、IL-8、IL-10、IL-13、IL-4受体、TNF-α和IFN-γ基因。
尽管BP患者更有可能携带IL-1β基因的-511T和-31C等位基因（P = 0.04），但在进行多重检验校正（Pc）后，该显著性消失。IL-1β基因的-511T和-31C等位基因之间存在完全连锁不平衡。在女性BP患者中与IL-1β（-511T）和（-31C）等位基因的关联更强（68%对40.6%，优势比 = 3.11，Pc = 0.006）。在BP患者和对照之间未发现其他细胞因子基因多态性的等位基因和基因型分布有显著差异。此外，未观察到与疾病累及范围（局限性或全身性）的关联。
IL-1β（-511）和（-31）多态性与女性BP显著相关。我们分析的细胞因子基因的其他遗传多态性在我们的中国人群中似乎与BP易感性无关。
