Mitochondrial COX3 and tRNA Gene Variants Associated with Risk and Prognosis of Idiopathic Pulmonary Fibrosis
Journal
International journal of molecular sciences
Journal Volume
26
Journal Issue
3
Start Page
Article number 1378
ISSN
1422-0067
Date Issued
2025-02-06
Author(s)
Chou, Wen-Ru
Liu, Wei-Lun
Kuo, Yen-Liang
Chang, Chih-Yueh
Chang, Hsiu-Ching
Liu, Jia-Luen
Lin, Chia-Nan
Chao, Ke-Yun
Tseng, Chi-Wei
Lee, I-Hsien
Abstract
Idiopathic pulmonary fibrosis (IPF) has been associated with mitochondrial dysfunction. We investigated whether mitochondrial DNA variants in peripheral blood leukocytes (PBLs), which affect proteins of the respiratory chain and mitochondrial function, could be associated with an increased risk and poor prognosis of IPF. From 2020 to 2022, we recruited 36 patients (age: 75.3 ± 8.5; female: 19%) with IPF, and 80 control subjects (age: 72.3 ± 9.0; female: 27%). The mitochondrial genome of peripheral blood leukocytes was determined using next-generation sequencing. During a 45-month follow-up, 10 (28%) patients with IPF remained stable and the other 26 (72%) progressed, with 12 (33%) mortalities. IPF patients had more non-synonymous (NS) variants (substitution/deletion/insertion) in mitochondrial gene (coding for subunit 3 of complex IV of the respiratory chain), and more mitochondrial tRNA variants located in the anticodon (AC) stem, AC loop, variable loop, T-arm, and T-loop of the tRNA clover-leaf structure in PBLs than the control group. The succumbed IPF patients were older, had lower initial diffusion capacity, and higher initial fibrosis score on high-resolution computerized tomography (HRCT) than the alive group. NS variants in mitochondrial gene and tRNA variants in PBLs were associated with shorter survival. Our study shows that (1) leukocyte mitochondrial NS variants are associated with risk and prognosis of IPF; (2) leukocyte mitochondrial tRNA variants located in the AC stem, AC loop, variable loop, T-arm, and T-loop of the tRNA clover-leaf structure are associated with risk, and the presence of tRNA variants is associated with poor prognosis of IPF.
Subjects
cytochrome c oxidase subunit 3 (COX3)
idiopathic pulmonary fibrosis (IPF)
mitochondrial DNA (mtDNA)
nonsynonymous variant
tRNA variant
SDGs
Type
journal article