Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4131-4137. doi: 10.3892/mmr.2017.8302. Epub 2017 Dec 18.
The advanced glycosylation end product-specific receptor (RAGE) has been demonstrated to be an important mediator of asthma pathogenesis. The soluble isoform of RAGE (sRAGE) acts as a 'decoy' to sequester RAGE ligands, and thus prevents their binding to the receptor. A number of reports have linked deficiency of sRAGE to the severity and outcomes of various human diseases, and association with RAGE G82S variants. However, whether sRAGE levels are increased or decreased in asthmatic patients is unclear. The aim of the present study was to determine plasma sRAGE levels in different asthma phenotypes and associations of plasma sRAGE levels with RAGE G82S variants. A total of 85 neutrophilic and 109 non‑neutrophilic newly diagnosed asthmatic patients, and 118 healthy controls, were recruited. Plasma sRAGE levels were measured by ELISA analysis. RAGE G82S genotypes were detected using the Sanger sequencing method. Plasma sRAGE levels were decreased in neutrophilic asthmatics (443.67±208.9 pg/ml) and increased in non‑neutrophilic asthmatics (677.63±300.75 pg/ml) compared with healthy controls (550.02±300.83 pg/ml) (P<0.001). Plasma sRAGE levels were positively correlated with FEV1% predicted (FEV1% Pre) (rp=0.258; P=0.023) in neutrophilic asthmatics. The frequency of G82S genotypes was significantly different between neutrophilic and non‑neutrophilic asthmatics (P=0.009). Neutrophilic asthmatics with genotypes A/G or A/A (389.83±150.37 and 264.59±161.74 pg/ml, respectively) had significantly decreased sRAGE levels compared with the G/G genotype (498.64±235.37 pg/ml) (P=0.022). Those with the A/G and A/A genotype (60.14±22.36%) displayed a trend toward lower FEV1% Pre compared with those with the G/G genotype (64.51±27.37%). No significant difference in sRAGE levels or an association with FEV1% Pre was observed between the different genotypes in non‑neutrophilic asthmatics. In conclusion, the results of the present study indicated that plasma sRAGE levels are altered in different asthma inflammatory phenotypes. Plasma sRAGE may be a biomarker of asthma severity and may be associated with G82S gene variants in neutrophilic asthmatics.
晚期糖基化终产物特异性受体（RAGE）已被证实是哮喘发病机制的重要介质。RAGE 的可溶性同工型（sRAGE）作为“诱饵”，与 RAGE 配体结合，从而阻止它们与受体结合。许多报道将 sRAGE 的缺乏与各种人类疾病的严重程度和结果以及与 RAGE G82S 变体相关联。然而，哮喘患者的 sRAGE 水平是增加还是减少尚不清楚。本研究旨在确定不同哮喘表型患者的血浆 sRAGE 水平，并确定血浆 sRAGE 水平与 RAGE G82S 变体的相关性。共招募了 85 名中性粒细胞性和 109 名非中性粒细胞性新诊断的哮喘患者和 118 名健康对照者。通过 ELISA 分析测定血浆 sRAGE 水平。使用 Sanger 测序法检测 RAGE G82S 基因型。与健康对照组（550.02±300.83pg/ml）相比，中性粒细胞性哮喘患者（443.67±208.9pg/ml）的血浆 sRAGE 水平降低，而非中性粒细胞性哮喘患者（677.63±300.75pg/ml）的血浆 sRAGE 水平升高（P<0.001）。在中性粒细胞性哮喘患者中，血浆 sRAGE 水平与 FEV1%预测值（FEV1%Pre）呈正相关（rp=0.258；P=0.023）。中性粒细胞性和非中性粒细胞性哮喘患者之间的 G82S 基因型频率存在显著差异（P=0.009）。与 G/G 基因型（498.64±235.37pg/ml）相比，基因型为 A/G 或 A/A 的中性粒细胞性哮喘患者（389.83±150.37 和 264.59±161.74pg/ml）的 sRAGE 水平显著降低（P=0.022）。与 G/G 基因型相比，具有 A/G 和 A/A 基因型的患者（60.14±22.36%）的 FEV1%Pre 呈下降趋势。非中性粒细胞性哮喘患者中，不同基因型之间的 sRAGE 水平无显著差异，也与 FEV1%Pre 无关联。综上所述，本研究结果表明，不同哮喘炎症表型患者的血浆 sRAGE 水平发生改变。血浆 sRAGE 可能是哮喘严重程度的生物标志物，与中性粒细胞性哮喘患者的 G82S 基因变异有关。
