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

2022; Multidisciplinary Digital Publishing Institute; Volume: 11; Issue: 13 Linguagem: Inglês

10.3390/cells11132121

2073-4409

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

Epigenetics and DNA Methylation

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.