AGER gene polymorphisms and soluble receptor for advanced glycation end product in patients with idiopathic pulmonary fibrosis

ABSTRACT Background and objective 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). Methods 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. Results 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). Conclusion 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. AGER rs2070600 polymorphism is frequent in patients with idiopathic pulmonary fibrosis (IPF). Reduced soluble receptor for advanced glycation end product (sRAGE) might be associated with poor prognosis of IPF. Our study suggests that RAGE and its polymorphism may be related to IPF and sRAGE is a potential prognostic marker for IPF.