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Hofbauer TM, Mangold A, Ondracek AS, et al. Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction. Basic Res Cardiol. 2021;116(1):29doi: 10.1007/s00395-021-00864-w.
Hofbauer, T. M., Mangold, A., Ondracek, A. S., Panzenböck, A., Scherz, T., Müller, J., Distelmaier, K., Seidl, V., Kastl, S., Müller-Nurasyid, M., Peters, A., Strauch, K., Winker, R., Wohlschläger-Krenn, E., Nistler, S., & Lang, I. M. (2021). Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction. Basic research in cardiology, 116(1), 29. https://doi.org/10.1007/s00395-021-00864-w
Hofbauer, Thomas M, et al. "Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction." Basic research in cardiology vol. 116,1 (2021): 29. doi: https://doi.org/10.1007/s00395-021-00864-w
Hofbauer TM, Mangold A, Ondracek AS, Panzenböck A, Scherz T, Müller J, Distelmaier K, Seidl V, Kastl S, Müller-Nurasyid M, Peters A, Strauch K, Winker R, Wohlschläger-Krenn E, Nistler S, Lang IM. Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction. Basic Res Cardiol. 2021 Apr 23;116(1):29. doi: 10.1007/s00395-021-00864-w. PMID: 33891165; PMCID: PMC8064981.
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Basic Res Cardiol. 2021 Apr 23;116(1):29. doi: 10.1007/s00395-021-00864-w.

Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

Basic research in cardiology

Thomas M Hofbauer, Andreas Mangold, Anna S Ondracek, Adelheid Panzenböck, Thomas Scherz, Julian Müller, Klaus Distelmaier, Veronika Seidl, Stefan Kastl, Martina Müller-Nurasyid, Annette Peters, Konstantin Strauch, Robert Winker, Evelyne Wohlschläger-Krenn, Sonja Nistler, Irene M Lang

Affiliations

  1. Department of Cardiology, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
  2. Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  3. IBE (Institute for Medical Information Processing, Biometry, and Epidemiology), Faculty of Medicine, LMU Munich, Munich, Germany.
  4. Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
  5. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany.
  6. Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  7. Chair of Genetic Epidemiology, Faculty of Medicine, IBE, LMU Munich, Munich, Germany.
  8. Health and Prevention Center, Sanatorium Hera, Löblichgasse 14, 1090, Vienna, Austria.
  9. Department of Cardiology, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. [email protected].

PMID: 33891165 PMCID: PMC8064981 DOI: 10.1007/s00395-021-00864-w

Abstract

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI.

Keywords: Deoxyribonuclease; Mortality; Neutrophil extracellular traps; ST-segment elevation myocardial infarction; Single nucleotide polymorphism

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