Pabst S, Baumgarten G, Stremmel A, Lennarz M, Knüfermann P, Gillissen A, Vetter H, Grohé C
Medizinische Universitäts-Poliklinik, Rheinische-Friedrich-Wilhelms-Universität Bonn, Wilhelmstrasse 35-37, D-53111 Bonn, Germany.
Clin Exp Immunol. 2006 Mar;143(3):420-6. doi: 10.1111/j.1365-2249.2006.03008.x.
The aetiology of sarcoidosis, an inflammatory granulomatous multi-system disorder, is unclear. It is thought to be the product of an unknown exogenous antigenic stimulus and an endogenous genetic susceptibility. Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Lipopolysaccharide (LPS), for example, binds to TLR 4. Two different polymorphisms for the TLR4 gene (Asp299Gly and Thr399Ile) have been described recently. This leads to a change in the extracellular matrix function of TLR4 and to impaired LPS signal transduction. We genotyped a total of 141 Caucasian patients with sarcoidosis and 141 healthy unrelated controls for the Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. Among sarcoidosis patients the prevalence for each Asp299Gly and Thr399Ile mutant allele was 15.6% (22/141). In the control group the prevalence was 5.67% (8/141) (P = 0.07). In the subgroup of patients with acute sarcoidosis there was no difference in the control group (P = 0.93), but there was a highly significant association between patients with a chronic course of sarcoidosis and TLR4 gene polymorphisms (P = 0.01).
结节病是一种炎症性肉芽肿多系统疾病，其病因尚不清楚。它被认为是未知外源性抗原刺激和内源性遗传易感性共同作用的结果。Toll样受体（TLR）是细胞对细菌细胞壁成分作出反应所必需的信号分子。例如，脂多糖（LPS）与TLR 4结合。最近发现了TLR4基因的两种不同多态性（Asp299Gly和Thr399Ile）。这导致TLR4的细胞外基质功能发生变化，并损害LPS信号转导。我们对141例白种人结节病患者和141名健康无关对照进行了TLR4基因Asp299Gly和Thr399Ile多态性的基因分型。通过聚合酶链反应随后进行限制性片段长度多态性（RFLP）分析来鉴定突变。在结节病患者中，Asp299Gly和Thr399Ile突变等位基因的患病率均为15.6%（22/141）。在对照组中，患病率为5.67%（8/141）（P = 0.07）。在急性结节病患者亚组中，与对照组无差异（P = 0.93），但结节病慢性病程患者与TLR4基因多态性之间存在高度显著关联（P = 0.01）。
