Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD.
Stefan KuhnertSiavash MansouriMichael A RiegerSoni Savai PullamsettiEdibe AvciGabriela Díaz-PiñaManju PadmasekarMario LoosoStefan HadzicTill AckerStephan KlattJochen WilhelmIngrid FlemingNatascha SommerNorbert WeissmannClaus VogelmeierRobert BalsAndreas ZeiherStefanie DimmelerWerner SeegerSoni Savai PullamsettiPublished in: Cells (2022)
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.
Keyphrases
- lung function
- chronic obstructive pulmonary disease
- dna methylation
- gene expression
- high throughput
- cystic fibrosis
- air pollution
- circulating tumor cells
- end stage renal disease
- risk factors
- chronic kidney disease
- oxidative stress
- induced apoptosis
- genome wide
- ejection fraction
- single cell
- cell proliferation
- fluorescent probe
- hematopoietic stem cell
- risk assessment