The PTPN22 620W allele is a risk factor for Wegener's granulomatosis
The PTPN22 620W allele is a risk factor for Wegener's granulomatosis
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DOI：
10.1002/art.21487
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Epplen, JT
中科院分区：
文献类型：
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作者：
Jagiello, P;Aries, P;Epplen, JT
Objective.对患有多种自身免疫性疾病的家族的分析揭示了细胞内酪氨酸磷酸酶基因PTPN22的功能多态性620W是1型糖尿病、血清阳性类风湿性关节炎、系统性红斑狼疮和桥本甲状腺炎的易感因素，PTPN22蛋白的存在似乎预示着这些疾病中自身抗体的发展。因此，本研究探讨了功能相关的PTPN22多态性是否与韦格纳肉芽肿病（WG）相关。在199例WG患者和399例健康个体中进行了一项基于人群的PTPN 22多态性研究。采用简单的限制性片段长度多态性分析方法对R620W基因进行分析。抗神经细胞胞浆抗体（ANCA）阳性WG患者PTPN22 620W等位基因频率显著高于健康对照组（P < 0.001）。这种关联在肾、肺、眼和周围神经系统受累的患者中尤其显著（即，结论：PTPN 22 620 W等位基因似乎参与WG的发病机制，ANCA阳性似乎是标志。
Objective. Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant PTPN22 polymorphism is associated with Wegener's granulomatosis (WG).Methods. A population-based study was performed for the PTPN22 polymorphism in 199 patients with WG and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis.Results. The PTPN22 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized WG).Conclusion. The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark.