4.6 Article

Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD

Journal

CELLS
Volume 11, Issue 13, Pages -

Publisher

MDPI
DOI: 10.3390/cells11132121

Keywords

clonal hematopoiesis; inflammation; COPD

Categories

Funding

  1. Max Planck Society
  2. Cardio-Pulmonary Institute (CPI)
  3. German Center for Lung Research (DZL)
  4. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [268555672-SFB 1213]
  5. European Research Council (ERC) Consolidator Grant [866051]
  6. European Research Council (ERC) [866051] Funding Source: European Research Council (ERC)

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This study found an increased incidence of CHIP mutations in COPD patients, which are associated with hypomethylation of PLD5, leading to elevated levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.
Chronic obstructive pulmonary disease (COPD) is a disease with an inflammatory phenotype with increasing prevalence in the elderly. Expanded population of mutant blood cells carrying somatic mutations is termed clonal hematopoiesis of indeterminate potential (CHIP). The association between CHIP and COPD and its relevant effects on DNA methylation in aging are mainly unknown. Analyzing the deep-targeted amplicon sequencing from 125 COPD patients, we found enhanced incidence of CHIP mutations (similar to 20%) with a predominance of DNMT3A CHIP-mediated hypomethylation of Phospholipase D Family Member 5 (PLD5), which in turn is positively correlated with increased levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.

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