Toll 样受体-4 和肿瘤坏死因子基因多态性对化脓性汗腺炎患者的影响。
Impact of Toll-like receptor-4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa.
机构信息
Fourth Department of Internal Medicine, ATTIKON University Hospital, 1, Rimini Str., P.C. 12462, Athens, Greece.
出版信息
Br J Dermatol. 2013 Feb;168(2):311-7. doi: 10.1111/bjd.12105.
BACKGROUND
Recent evidence has suggested that deranged immune responses play a role in the pathogenesis of hidradenitis suppurativa (HS).
OBJECTIVES
To investigate the role of single nucleotide polymorphisms (SNPs) of the tumour necrosis factor (TNF) and Toll-like receptor 4 (TLR4) genes in the physical course of HS; these genes encode for proteins implicated in the immune response of the host.
METHODS
DNA was isolated from 190 patients with HS and 84 healthy controls. SNPs at the promoter regions -376G/A, -238G/A and -308G/A of the TNF gene and the Asp299Gly and Thr399Ile SNPs of the TLR4 gene were determined by polymerase chain reaction (PCR) and digestion of the PCR product by restriction enzymes; after electrophoresis on 2·0% agarose gel, products were visualized on under ultraviolet radiation.
RESULTS
The presence of the -238 TNF gene polymorphism was associated with a predisposition to HS (P = 0·027). Susceptibility to the disease was strongly correlated with the presence of AGG/GGA/AGA/GAA TNF haplotypes in 32 (17%) patients compared with two (2%) controls (P < 0·001, odds ratio 8·30, 95% confidence interval 1·94-35·52). The frequency of HS exacerbations and disease severity were greater in patients carrying any of the GAG/AGG/GGA/AGA/GAA haplotypes of the TNF gene. Thirty-two patients were given TNF antagonists. Nineteen of these patients were carriers of the GGG haplotype of the TNF gene, whereas 13 were carriers of other haplotypes; favourable responses as evidenced by the Sartorius score were registered in 15 (79%) and five (38%, P = 0·025), respectively. Carriage of the TLR4 gene alleles was not associated with any disease parameter.
CONCLUSIONS
A significant role of SNPs at the promoter region of the TNF gene is indicated for susceptibility to HS and for response to TNF antagonists.
背景
最近的证据表明，紊乱的免疫反应在化脓性汗腺炎（HS）的发病机制中起作用。
目的
研究肿瘤坏死因子（TNF）和 Toll 样受体 4（TLR4）基因的单核苷酸多态性（SNP）在 HS 病程中的作用；这些基因编码宿主免疫反应中涉及的蛋白质。
方法
从 190 例 HS 患者和 84 例健康对照中提取 DNA。采用聚合酶链反应（PCR）和限制性内切酶消化 PCR 产物的方法检测 TNF 基因启动子区域-376G/A、-238G/A 和-308G/A 以及 TLR4 基因的 Asp299Gly 和 Thr399Ile SNPs；在 2.0%琼脂糖凝胶上电泳后，在紫外线下观察产物。
结果
-238TNF 基因多态性的存在与 HS 的易感性有关（P=0.027）。与 2 名对照（2%）相比，32 名（17%）患者中存在 AGG/GGA/AGA/GAA TNF 单体型，与疾病易感性密切相关（P<0.001，优势比 8.30，95%置信区间 1.94-35.52）。携带 TNF 基因任何 GAG/AGG/GGA/AGA/GAA 单体型的患者 HS 加重和疾病严重程度更大。32 例患者接受 TNF 拮抗剂治疗。19 例患者携带 TNF 基因 GGG 单体型，而 13 例携带其他单体型；Sartorius 评分证实，15 例（79%）和 5 例（38%）患者有良好反应（P=0.025）。TLR4 基因等位基因的携带与任何疾病参数无关。
结论
TNF 基因启动子区域 SNP 对 HS 的易感性和对 TNF 拮抗剂的反应具有重要作用。
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