Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.
Aged
Austria
Case-Control Studies
Deoxyribonuclease I
/ genetics
Extracellular Traps
/ metabolism
Female
Genetic Association Studies
Germany
Heterozygote
Homozygote
Humans
Male
Middle Aged
Percutaneous Coronary Intervention
Polymorphism, Single Nucleotide
Prognosis
Risk Assessment
Risk Factors
ST Elevation Myocardial Infarction
/ genetics
Time Factors
Deoxyribonuclease
Mortality
Neutrophil extracellular traps
ST-segment elevation myocardial infarction
Single nucleotide polymorphism
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
23 04 2021
23 04 2021
Historique:
received:
07
09
2020
accepted:
18
03
2021
entrez:
23
4
2021
pubmed:
24
4
2021
medline:
15
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33891165
doi: 10.1007/s00395-021-00864-w
pii: 10.1007/s00395-021-00864-w
pmc: PMC8064981
doi:
Substances chimiques
DNASE1 protein, human
EC 3.1.21.1
Deoxyribonuclease I
EC 3.1.21.1
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
29Subventions
Organisme : Austrian Science Fund
ID : SFB-F54
Organisme : Ludwig-Maximilians-Universität
ID : LMUinnovativ
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