Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Respirology. 2017 Jul;22(5):965-971. doi: 10.1111/resp.12995. Epub 2017 Feb 14.
The receptor for advanced glycation end product (RAGE) is a multiligand cell-surface receptor abundantly expressed in the lung. RAGE/ligand interaction has been postulated to participate in the pathogenesis of inflammatory diseases, while soluble RAGE (sRAGE) might act as a decoy receptor. A functional polymorphism rs2070600 in the gene coding RAGE (AGER) might modulate its receptor function. The aim of this study was to investigate the association of AGER polymorphisms and circulatory sRAGE with the development and progression of idiopathic pulmonary fibrosis (IPF).
This study comprised 87 Japanese patients with IPF and 303 healthy controls. Seven tag polymorphisms in AGER were genotyped and their distributions were compared. We also measured serum sRAGE levels, and evaluated the correlations of sRAGE levels with AGER polymorphisms and the prognosis of the patients with IPF.
The frequency of AGER rs2070600 genotype with minor allele was significantly higher in patients with IPF (OR = 1.84, 95% CI = 1.08-3.10). Additionally, the carriage of the rs2070600 minor allele and the presence of IPF were independently associated with reduced serum levels of sRAGE. Moreover, reduced sRAGE (≤471.8 pg/mL) was related to acute exacerbation of IPF and was an independent predictor of 5-year survival in patients with the disease (hazard ratio (HR) = 7.956, 95% CI = 1.575-53.34).
These results suggest a possible association between a functional polymorphism in AGER and IPF disease susceptibility, and indicate a potential prognostic value of circulatory sRAGE.
晚期糖基化终产物受体（RAGE）是一种在肺部大量表达的多配体细胞表面受体。RAGE/配体相互作用被认为参与了炎症性疾病的发病机制，而可溶性 RAGE（sRAGE）可能作为一种诱饵受体发挥作用。编码 RAGE（AGER）的基因中的功能性多态性 rs2070600 可能调节其受体功能。本研究旨在探讨 AGER 多态性与循环 sRAGE 与特发性肺纤维化（IPF）的发生和进展的关系。
本研究纳入了 87 例日本 IPF 患者和 303 例健康对照者。对 AGER 中的 7 个标签多态性进行了基因分型，并比较了它们的分布。我们还测量了血清 sRAGE 水平，并评估了 sRAGE 水平与 AGER 多态性及 IPF 患者预后的相关性。
IPF 患者中 AGER rs2070600 基因型携带 minor 等位基因的频率明显升高（OR = 1.84，95% CI = 1.08-3.10）。此外，携带 rs2070600 minor 等位基因和存在 IPF 与血清 sRAGE 水平降低独立相关。此外，sRAGE 降低（≤471.8 pg/mL）与 IPF 的急性加重有关，并且是该疾病患者 5 年生存率的独立预测因素（危险比（HR）= 7.956，95% CI = 1.575-53.34）。
这些结果提示 AGER 中的功能性多态性与 IPF 疾病易感性之间可能存在关联，并表明循环 sRAGE 具有潜在的预后价值。
