Your browser doesn't support javascript.
loading
Prevalence and prognostic significance of DNMT3A- and TET2- clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction.
Wang, Shengfang; Hu, Sining; Luo, Xing; Bao, Xiaoyi; Li, Ji; Liu, Minghao; Lv, Ying; Zhao, Chen; Zeng, Ming; Chen, Xi; Unsworth, Amanda; Jones, Sarah; Johnson, Thomas W; White, Stephen J; Jia, Haibo; Yu, Bo.
Afiliación
  • Wang S; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Hu S; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Luo X; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Bao X; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Li J; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Liu M; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Lv Y; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Zhao C; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Zeng M; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Chen X; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China.
  • Unsworth A; Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK.
  • Jones S; Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK.
  • Johnson TW; Department of Cardiology, Bristol Heart Institute, Upper Maudlin St., Bristol BS2 8HW, UK.
  • White SJ; Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK.
  • Jia H; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China. Electronic address: jhb101180@163.com.
  • Yu B; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China. Electronic address: yubodr@163.com.
EBioMedicine ; 78: 103964, 2022 Apr.
Article en En | MEDLINE | ID: mdl-35339897
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-1ß, 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-1ß (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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dioxigenasas / Proteínas de Unión al ADN / Infarto del Miocardio con Elevación del ST / ADN Metiltransferasa 3A Tipo de estudio: Diagnostic_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: EBioMedicine Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dioxigenasas / Proteínas de Unión al ADN / Infarto del Miocardio con Elevación del ST / ADN Metiltransferasa 3A Tipo de estudio: Diagnostic_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: EBioMedicine Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos