High-sensitivity C-reactive protein is associated with clonal hematopoiesis of indeterminate potential
Open accessAbstract
Clonal hematopoiesis of indeterminate potential (CHIP) is predictive of hematological cancers and cardiovascular diseases, but the etiology of CHIP initiation and clonal expansion is unknown. Several lines of evidence suggest that proinflammatory cytokines may favor mutated hematopoietic stem cell expansion. To investigate the potential link between inflammation and CHIP, we performed targeted deep sequencing of 11 genes previously implicated in CHIP in 1887 subjects aged >70 years from the Montreal Heart Institute Biobank, of which 1359 had prior coronary artery disease (CAD), and 528 controls did not. We assessed association of CHIP with log transformed high-sensitivity C-reactive protein (hs-CRP), a validated biomarker of inflammation. CHIP was identified in 427 of the 1887 subjects (22.6%). CHIP mutations were more frequently identified in DNMT3A (11.6%) and TET2 (6.1%), with a higher proportion of TET2 mutations occurring in controls than in patients with CAD (9.0% vs 4.9%, P < .001). CHIP carriers had 21% higher hs-CRP levels compared with their noncarrier counterparts (eβ = 1.21, 95% confidence interval [CI]: 1.08 to 1.36; P = .001). A similar effect was observed in the subgroup of patients with known CAD (eβ = 1.22, 95% CI: 1.06 to 1.41; P = .005). These findings confirm the association between inflammation and CHIP. This association may open investigational avenues aimed at documenting mechanisms linking inflammation to clonal progression and ultimately supports prev…
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The Montreal Heart Institute Biobank study identified increased C-reactive protein levels in all CH carriers irrespective of the mutated gene involved.
“The Montreal Heart Institute Biobank study identified increased C-reactive protein levels, a nonspecific marker of systemic inflammation, in all CH carriers irrespective of the mutated gene involved [60].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [60]
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“In a cohort of patients with ulcerative colitis, Zhang et al documented a small but significantly increased level of serum IFN-g but not TNF-a in subjects with DNMT3A mutation.(39) Therefore, it is possible that the small but long-standing difference in inflammation level may have a biological impact.”
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Clonal hematopoiesis and inflammation – the perpetual cycle
Avagyan, S., & Zon, L. I. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.12.001 · Cited by 79 · see citing works
- Authors
- Busque, L., Sun, M., Buscarlet, M., Ayachi, S., Feroz Zada, Y., Provost, S., Bourgoin, V., Mollica, L., Meisel, M., Hinterleitner, R., Jabri, B., Dubé, M.-P., & Tardif, J.-C.
- Affiliations
- Hôpital Maisonneuve-Rosemont (CA)
- Montreal Heart Institute (CA)
- Research Center,
- Université de Montréal (CA)
- Beaulieu-Saucier Pharmacogenomics Center, Montreal Heart Institute, Montreal, Canada;
- University of Pittsburgh (US)
- Department of Medicine, University of Chicago, Chicago, IL
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-06-03
- Volume
- 4
- Issue
- 11
- Pages
- 2430-2438
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC7284088
- OpenAlex
- W3032758825
- Cited by
- 87
- References
- 9
- Citations by year
- 2026: 2 · 2025: 18 · 2024: 14 · 2023: 14 · 2022: 20 · 2021: 11 · 2020: 7 · 2019: 1
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- clonal hematopoiesis of indeterminate potential, high-sensitivity C-reactive protein, inflammation, coronary artery disease, DNMT3A mutation, TET2 mutation, clonal expansion, cardiovascular risk
- MeSH terms
- Clonal Hematopoiesis, Aged, Angiotensin-Converting Enzyme Inhibitors, C-Reactive Protein, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Angiotensin Receptor Antagonists, Percutaneous Coronary Intervention
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