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Lookup NU author(s): Dr Stephen WhiteORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022 The Author(s)Background: Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Methods: Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. Findings: Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4–3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103–3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154–2.912, P = 0.010). Concentrations of plasma IL-1β (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group. Interpretation: DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers. Funding: National Natural Science Foundation of China; National Key R&D Program of China.
Author(s): Wang S, Hu S, Luo X, Bao X, Li J, Liu M, Lv Y, Zhao C, Zeng M, Chen X, Unsworth A, Jones S, Johnson TW, White SJ, Jia H, Yu B
Publication type: Article
Publication status: Published
Journal: eBioMedicine
Year: 2022
Volume: 78
Print publication date: 01/04/2022
Online publication date: 24/03/2022
Acceptance date: 09/03/2022
Date deposited: 07/11/2023
ISSN (electronic): 2352-3964
Publisher: The Lancet Publishing Group
URL: https://doi.org/10.1016/j.ebiom.2022.103964
DOI: 10.1016/j.ebiom.2022.103964
PubMed id: 35339897
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