Ates O, Müsellim B, Ongen G, Topal-Sarikaya A
Department of Molecular Biology and Genetics, Science Faculty, Istanbul University, 34118 Vezneciler, Istanbul, Turkey.
J Clin Immunol. 2008 Jan;28(1):73-7. doi: 10.1007/s10875-007-9134-7. Epub 2007 Sep 18.
Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5' promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3'UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.
系统性硬化症（SSc），也称为“硬皮病”，是一种病因不明的进行性全身性疾病，其特征为过度纤维化、血管异常和免疫功能障碍。Nramp 1基因对巨噬细胞激活途径具有多种多效性作用，包括趋化因子/细胞因子基因KC、肿瘤坏死因子α、白细胞介素-1β、诱导型一氧化氮合酶的上调，以及主要组织相容性复合体II类表达，还有肿瘤活性和抗菌活性。所有这些多效性作用对于抗感染都很重要，但它们也可能参与自身免疫性疾病的诱导和维持。我们分析了52例有间质性肺受累的系统性硬化症患者和136名健康对照者的四种天然抗性相关巨噬细胞蛋白1（NRAMP1）基因多态性，包括5'启动子（GT）n微卫星、INT4（469 + 14G/C）、3'非翻译区（1729 + 55del4）和D543N（密码子543，天冬氨酸到天冬酰胺）。我们发现INT4、（GT）n多态性（分别为p = 0.006和0.027）与系统性硬化症之间存在显著关联。我们的研究结果表明，NRAMP1是系统性硬化症一个合理的候选基因。
