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PARK2 as a susceptibility factor for nontuberculous mycobacterial pulmonary disease

Authors
 Youngmok Park  ;  Ji Won Hong  ;  Eunsol Ahn  ;  Heon Yung Gee  ;  Young Ae Kang 
Citation
 RESPIRATORY RESEARCH, Vol.25(1) : 310, 2024-08 
Journal Title
RESPIRATORY RESEARCH
ISSN
 1465-9921 
Issue Date
2024-08
MeSH
Aged ; Female ; Genetic Predisposition to Disease* / genetics ; Humans ; Lung Diseases / diagnosis ; Lung Diseases / genetics ; Lung Diseases / microbiology ; Male ; Middle Aged ; Mycobacterium Infections, Nontuberculous* / diagnosis ; Mycobacterium Infections, Nontuberculous* / epidemiology ; Mycobacterium Infections, Nontuberculous* / genetics ; Ubiquitin-Protein Ligases* / genetics
Keywords
Autophagy ; Gene expression profiling ; Nontuberculous mycobacteria ; Ubiquitination
Abstract
Background: The genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.

Methods: Peripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls). Differentially expressed genes (DEGs) were identified by RNA sequencing and subjected to functional enrichment and immune cell deconvolution analyses.

Results: We enrolled 48 participants, including 26 patients with NTM-PD (median age, 58.0 years; 84.6% female), and 22 healthy controls (median age, 58.5 years; 90.9% female). We identified 21 upregulated and 44 downregulated DEGs in the NTM-PD group compared to those in the control group. NTM infection did not have a significant impact on gene expression in the NTM-PD group compared to the control group, and there were no differences in the proportion of immune cells. However, through gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, we discovered that PARK2 is a key factor associated with NTM-PD. The PARK2 gene, which is linked to the ubiquitination pathway, was downregulated in the NTM-PD group (fold change, - 1.314, P = 0.047). The expression levels of PARK2 remained unaltered after favorable treatment outcomes, suggesting that the gene is associated with host susceptibility rather than with the outcomes of infection or inflammation. The area under the receiver operating characteristic curve for the PARK2 gene diagnosing NTM-PD was 0.813 (95% confidence interval, 0.694-0.932).

Conclusion: We identified the genetic signatures associated with NTM-PD in a cohort of Korean patients. The PARK2 gene presents as a potential susceptibility factor in NTM-PD .
Files in This Item:
T202405256.pdf Download
DOI
39143598
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Ae(강영애) ORCID logo https://orcid.org/0000-0002-7783-5271
Park, Youngmok(박영목) ORCID logo https://orcid.org/0000-0002-5669-1491
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/200474
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