Clinical and genetic features of idiopathic pulmonary fibrosis in a Korean cohort

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is characterized by substantial genetic heterogeneity across populations, yet genetic features in Asian populations remain underexplored. This study aimed to describe the clinical and genetic landscape of Korean IPF patients and compare findings with reference populations. Methods The authors analyzed 107 Korean IPF patients from Severance Hospital (2012-2023), including 19 (17.8%) with family history of IPF. Genomic DNA was genotyped using Illumina Multi-Ethnic Genotyping Array. Allele frequencies of 28 IPF-associated SNPs were compared to global and Korean reference populations, and variants within 29 IPF-related genes were analyzed by Fisher's exact tests. Clinical outcomes (survival and longitudinal lung function) were compared between familial and sporadic IPF using Kaplan-Meier and mixed-effects models. Results Among 107 Korean IPF patients (19 familial, 88 sporadic), three notable findings emerged. First, population-specific SNP differences were observed, with significant depletion of IPF risk variants such as TERT rs2736100 and FAM13A rs2609255 compared with Korean and global reference populations. Second, familial IPF cases showed significantly faster physiological decline, with greater reductions in FVC (-2.36%/year) and DLCO (-4.44%/year), although survival differences were not statistically significant. Third, systematic variant analysis identified 22 potentially pathogenic variants across 7 IPF-related genes, with the highest proportion in epithelial-mesenchymal transition (45.5%) and DNA repair/telomere maintenance (27.3%) pathways, in contrast to the surfactant gene-driven architecture frequently reported in Western cohorts. Conclusions This descriptive study outlines the clinical and genetic features of Korean IPF patients, highlighting population-specific genomic patterns, more rapid physiological decline in familial cases, and a diverse distribution of potentially pathogenic variants. These findings underscore the importance of incorporating diverse populations into IPF genetic research to refine understanding of disease mechanisms and to inform the development of population-appropriate therapeutic strategies.