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Different Biological Pathways Are Up-regulated in the Elderly With Asthma: Sputum Transcriptomic Analysis

Allergy, Asthma & Immunology Research : AAIR 2019년 11권 1호 p.104 ~ 115
 ( Kim Byung-Keun ) - Korea University Medical Center Anam Hospital Department of Internal Medicine

 ( Lee Hyun-Seung ) - Seoul National University College of Medicine Department of Internal Medicine
 ( Sohn Kyoung-Hee ) - Kyung Hee University Medical Center Department of Internal Medicine
 ( Lee Suh-Young ) - Seoul National University College of Medicine Department of Internal Medicine
 ( Cho Sang-Heon ) - Seoul National University College of Medicine Department of Internal Medicine
 ( Park Heung-Woo ) - Seoul National University College of Medicine Department of Internal Medicine

Abstract

Background: Elderly asthma (EA) is increasing, but the pathogenesis is unclear. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells.

Methods: A total of 3,156 gene probes with significantly differential expressions between EA and healthy elderly controls were used for a hierarchical clustering of genes to identify gene clusters. Gene set enrichment analysis provided biological information, with replication from Gene Expression Omnibus expression profiles.

Results: Fifty-five EA patients and 10 elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n = 35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n = 20). The replication data set also identified 2 gene clusters (clusters 1' and 2'). Among 5 gene sets significantly enriched in cluster 1 and 3 gene sets significantly enriched in cluster 2, we confirmed that 2 were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION gene set in cluster 1 and EPITHELIAL MESENCHYMAL TRANSITION gene set in cluster 2').

Conclusions: The findings of 2 distinct gene clusters in EA and different biological pathways in each gene cluster suggest 2 different pathogenesis mechanisms underlying EA.

키워드

Asthma; Cluster analysis; Elderly; Gene expression
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