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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.*

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

Basic Res. Cardiol. 116:29 (2021)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Deoxyribonuclease ; Mortality ; Neutrophil Extracellular Traps ; St-segment Elevation Myocardial Infarction ; Single Nucleotide Polymorphism
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0300-8428
e-ISSN 1435-1803
Journal Basic Research in Cardiology
Quellenangaben Volume: 116, Issue: 1, Pages: , Article Number: 29 Supplement: ,
Publisher Springer
Publishing Place Tiergartenstrasse 17, D-69121 Heidelberg, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-504000-010
Grants Austrian Science Fund
Ludwig-Maximilians-Universitat
DOI 10.1007/s00395-021-00864-w
WOS ID WOS:000642913600002
Scopus ID 85104788360
PubMed ID 33891165
Erfassungsdatum 2021-06-10
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