IL13 Promoter (−1055) Polymorphism Associated with Leukocyte Mitochondria DNA Copy Number in Chronic Obstructive Pulmonary Disease

Abstract

IL13 polymorphism is associated with chronic obstructive pulmonary disease (COPD). Patients with COPD have smaller numbers of mitochondria deoxyribonucleic acid copies (mtDNA-CN) than people without COPD do. However, whether IL13 polymorphism affects the mutation and recombination of mitochondria remains unclear. Data for patients with COPD and non-COPD were collected from Kaohsiung Chang Gung Memorial Hospital to enable a comparison of their leukocyte mtDNA-CN and the association of this information with IL-13 promoter (−1055) polymorphism. This study included 99 patients with COPD and 117 individuals without COPD. The non-COPD individuals included 77 healthy individuals that never smoked and 40 healthy smokers. The patients with COPD exhibited significantly lower mtDNA-CN than non-COPD did (250.34 vs. 440.03; p < 0.001); mtDNA-CN was particularly pronounced in individuals with the IL13 CC and CT genotypes compared with individuals with the TT genotype. When only individuals without COPD were considered and when all participants were considered, the differences in the mtDNA-CNs in individuals with the CC and CT genotypes were more significant than those in individuals with the TT genotype (448.4 and 533.6 vs. 282.8; p < 0.05 in non-COPD group); (368.8 and 362.6 vs. 249.6, p < 0.05 in all participants). The increase mtDNA-CN in the CC and CT genotypes was also more than that in the TT genotype in COPD patients, but showed no significance (260.1 and 230.5 vs. 149.9; p = 0.343). The finding shows that COPD is a mitochondria regulatory disorder and IL-13 promoter (−1055) polymorphism is associated with leukocyte mtDNA-CN. Developing COPD control methods based on mitochondrial regulation will be possible.

Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus

“…Liu et al demonstrated that COPD patients have a lower leukocyte mtDNA copy number than nonsmoker or non-COPD patients [26]. His study also showed that the IL-13 promoter (−1055) polymorphism is associated with leukocyte mtDNA copy number [27]. The sequencing of a complete mitochondrial genome of a rat chronic obstructive pulmonary disease strain, with a length of 16,310 bp and coding for 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes, provides valuable insights into potential mitochondrial DNA mutations as markers in cancer and other diseases [28].…”

“…Large-scale, multicenter studies are essential to validate findings and establish robust associations. Additionally, understanding the interactions between nuclear and mitochondrial genomes and their collective impact on COPD susceptibility requires further exploration [27]. As we delve deeper into the realm of mitochondrial genetics in COPD, integrating these insights with clinical parameters and environmental influences becomes crucial.…”

COPD and biologic treatment: state of the art

“…IL-4 and IL-13 have many functions in the lungs, primarily in the regulation of inflammatory immune responses as well as mucus secretion [ [33][34][35][36]. Some genes, including IL13 polymorphism, have been associated with COPD [37,38] although studies are controversial. IL-13 binds to the IL-13 receptor alpha1 (IL-13a1) and induces recruitment of IL-4 receptor alpha 1 (IL-4Ra1), forming a complex responsible for the activation of signalling pathways [33].…”