Cells (Jul 2022)

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

  • Stefan Kuhnert,
  • Siavash Mansouri,
  • Michael A. Rieger,
  • Rajkumar Savai,
  • Edibe Avci,
  • Gabriela Díaz-Piña,
  • Manju Padmasekar,
  • Mario Looso,
  • Stefan Hadzic,
  • Till Acker,
  • Stephan Klatt,
  • Jochen Wilhelm,
  • Ingrid Fleming,
  • Natascha Sommer,
  • Norbert Weissmann,
  • Claus Vogelmeier,
  • Robert Bals,
  • Andreas Zeiher,
  • Stefanie Dimmeler,
  • Werner Seeger,
  • Soni S. Pullamsetti

DOI
https://doi.org/10.3390/cells11132121
Journal volume & issue
Vol. 11, no. 13
p. 2121

Abstract

Read online

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 (~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.

Keywords