The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients
The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients
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DOI：
10.1038/s41598-020-69184-8
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发表时间：
2020-07-30
影响因子：
4.6
通讯作者：
Hanaoka，Masayuki
中科院分区：
文献类型：
--
作者：
Kinjo，Takumi;Kitaguchi，Yoshiaki;Hanaoka，Masayuki
合并肺纤维化和肺气肿(CPFE)的主要发病机制仍未解决。晚期糖基化终产物受体(RAGE)在肺组织中高度表达，并与不同的多个配体相互作用，提示其与某些肺部疾病有关。为探讨慢性阻塞性肺疾病(CPFE)的发病机制，采用StepOne实时荧光定量聚合酶链式反应(SNP)技术，对111例CPFE患者和337例慢性阻塞性肺疾病(COPD)患者的RAGE基因3个单核苷酸多态性(rs2070600、rs1800625和rs2853807)进行了基因分型。采用双抗体夹心法测定血清可溶性RAGE(SRAGE)。我们发现rs2070600的等位基因频率在两组间有显著差异[校正P(Pc) = 0.015]。此外，在显性效应模型中，次要等位基因与慢性阻塞性肺疾病患者相比与慢性阻塞性肺疾病患者相关(优势比 = 为1.93；Pc = 为0.018)。此外，慢性阻塞性肺疾病组血清sRAGE水平显著低于慢性阻塞性肺病组(P = 0.014)。Rs2070600等位基因与慢性阻塞性肺功能衰竭患者血清sRAGE水平降低显著相关，并独立影响该组患者sRAGE水平降低(P = 0.020)。我们的结论是，AGERrs2070600微小等位基因(Gly82Ser突变)与日本患者CPFE肺纤维化的发病机制有关。
The dominant pathogenesis underlying the combined pulmonary fibrosis and emphysema (CPFE) remains unresolved. The receptor for advanced glycation end-products (RAGE) is highly expressed in lung tissues and interacts with distinct multiple ligands, implicating it in certain lung diseases. To elucidate the pathogenesis of CPFE, we genotyped three single nucleotide polymorphisms (SNPs: rs2070600, rs1800625, and rs2853807) of the gene encoding RAGE (AGER) in 111 CPFE patients and 337 chronic obstructive pulmonary disease (COPD) patients of Japanese by using StepOne Real-Time PCR System for SNP genotyping assay. Serum levels of soluble RAGE (sRAGE) were measured by ELISA. We found that the allele frequency of rs2070600 was significantly different between the two groups [corrected P (Pc) = 0.015]. In addition, the minor allele was associated with CPFE patients relative to COPD patients in a dominant effect model (Odds Ratio = 1.93; Pc = 0.018). Moreover, the serum sRAGE level was significantly lower in the CPFE group than the COPD group (P = 0.014). The rs2070600 minor allele was significantly associated with reduced sRAGE level in CPFE patients and independently affected sRAGE level reduction in this group (P = 0.020). We concluded that theAGERrs2070600 minor allele (Gly82Ser mutation) is associated with the pathogenesis of pulmonary fibrosis in CPFE in Japanese patients.