SNPs in the DNase 1 Gene Impair Its Activity and Are Increased in a STE-ACS Patient Cohort Compared to Healthy Controls

NCT02615015 | Unknown

• 1 other identifier: 1947/2014
• Study Type: observational
• Target: 800
• Locations: 0 countries
• Sites: N/A

Brief Summary

Neutrophil extracellular traps (NETs) and deoxyribonuclease (DNase) activity determine outcome in ST elevation acute coronary syndrome (STE-ACS). DNase single nucleotide polymorphisms (SNPs) were increased in a japanese cohort. In the present study, the investigators seek to measure DNase SNPs frequency in a caucasian STE-ACS cohort compared to healthy controls (each n=400). The investigators will compute polymorphisms, DNase activity, NET surrogate markers and clinical variables in regression models.

Conditions

ST Elevation Myocardial Infarction

Keywords

Deoxyribonuclease

Outcome Measures

Primary Outcomes (1)

• Frequency of SNPs of the DNase 1 and DNase gamma genes in the STE-ACS patient population compared to healthy controls

  through study completion, an average of 2 years

Secondary Outcomes (7)

• Correlation of SNPs of the DNase 1 and gamma gene with DNase activity

  through study completion, an average of 2 years

• Correlation of SNPs with major adverse cardiac events

  through study completion, an average of 2 years

• Correlation of DNAse activity with major adverse cardiac events

  through study completion, an average of 2 years

• Correlation of SNPs with DNA-Histone complex levels

  through study completion, an average of 2 years

• Correlation of SNPs with MPO-DNA complex levels

  through study completion, an average of 2 years

Study Arms (2)

ST elevation myocardial infarction patient cohort

Patients who suffered from ST elevation myocardial infarction since 2006, referred to the General Hospital of Vienna and received primary percutaneous coronary intervention.

Other: Blood draw

Healthy proband cohort

Age matched healthy individuals who voluntarily participate in the study.

Other: Blood draw

Interventions

Blood draw OTHER

Healthy proband cohort; ST elevation myocardial infarction patient cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

ST elevation myocardial infarction patients, who have been hospitalized in the General Hospital of Vienna since 2006 for ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention (pPCI) with TIMI 0-1.

You may qualify if:

• Medical history
• Detailed clinical examination
• Electrocardiography
• Echocardiography
• Routine blood draw (differential blood count, clotting factors including fibrinogen, liver enzymes, creatine kinase (CK), CK-MB, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), HbA1c
• Blood draw for research experiments

You may not qualify if:

• Patients under 18 years; auto-immune disease, immune-modulating medication, systemic infection

Sponsors & Collaborators

• Medical University of Vienna: lead

Related Publications (10)

• Nichols M, Townsend N, Scarborough P, Rayner M. Trends in age-specific coronary heart disease mortality in the European Union over three decades: 1980-2009. Eur Heart J. 2013 Oct;34(39):3017-27. doi: 10.1093/eurheartj/eht159. Epub 2013 Jun 25.

  PMID: 23801825 BACKGROUND

• Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005 Apr 21;352(16):1685-95. doi: 10.1056/NEJMra043430. No abstract available.

  PMID: 15843671 BACKGROUND

• Mangold A, Alias S, Scherz T, Hofbauer M, Jakowitsch J, Panzenbock A, Simon D, Laimer D, Bangert C, Kammerlander A, Mascherbauer J, Winter MP, Distelmaier K, Adlbrecht C, Preissner KT, Lang IM. Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res. 2015 Mar 27;116(7):1182-92. doi: 10.1161/CIRCRESAHA.116.304944. Epub 2014 Dec 29.

  PMID: 25547404 BACKGROUND

• Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15880-5. doi: 10.1073/pnas.1005743107. Epub 2010 Aug 23.

  PMID: 20798043 BACKGROUND

• Borissoff JI, Joosen IA, Versteylen MO, Brill A, Fuchs TA, Savchenko AS, Gallant M, Martinod K, Ten Cate H, Hofstra L, Crijns HJ, Wagner DD, Kietselaer BLJH. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):2032-2040. doi: 10.1161/ATVBAHA.113.301627. Epub 2013 Jul 1.

  PMID: 23818485 BACKGROUND

• Napirei M, Ludwig S, Mezrhab J, Klockl T, Mannherz HG. Murine serum nucleases--contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). FEBS J. 2009 Feb;276(4):1059-73. doi: 10.1111/j.1742-4658.2008.06849.x. Epub 2009 Jan 16.

  PMID: 19154352 BACKGROUND

• Ueki M, Takeshita H, Fujihara J, Iida R, Yuasa I, Kato H, Panduro A, Nakajima T, Kominato Y, Yasuda T. Caucasian-specific allele in non-synonymous single nucleotide polymorphisms of the gene encoding deoxyribonuclease I-like 3, potentially relevant to autoimmunity, produces an inactive enzyme. Clin Chim Acta. 2009 Sep;407(1-2):20-4. doi: 10.1016/j.cca.2009.06.022. Epub 2009 Jun 24.

  PMID: 19559017 BACKGROUND

• Ueki M, Kimura-Kataoka K, Takeshita H, Fujihara J, Iida R, Sano R, Nakajima T, Kominato Y, Kawai Y, Yasuda T. Evaluation of all non-synonymous single nucleotide polymorphisms (SNPs) in the genes encoding human deoxyribonuclease I and I-like 3 as a functional SNP potentially implicated in autoimmunity. FEBS J. 2014 Jan;281(1):376-90. doi: 10.1111/febs.12608. Epub 2013 Dec 10.

  PMID: 24206041 BACKGROUND

• Kumamoto T, Kawai Y, Arakawa K, Morikawa N, Kuribara J, Tada H, Taniguchi K, Tatami R, Miyamori I, Kominato Y, Kishi K, Yasuda T. Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients. Eur Heart J. 2006 Sep;27(17):2081-7. doi: 10.1093/eurheartj/ehl177. Epub 2006 Jul 28.

  PMID: 16877481 BACKGROUND

• Crimi G, Pica S, Raineri C, Bramucci E, De Ferrari GM, Klersy C, Ferlini M, Marinoni B, Repetto A, Romeo M, Rosti V, Massa M, Raisaro A, Leonardi S, Rubartelli P, Oltrona Visconti L, Ferrario M. Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC Cardiovasc Interv. 2013 Oct;6(10):1055-63. doi: 10.1016/j.jcin.2013.05.011.

  PMID: 24156966 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood draw, DNA isolation, plasma isolation

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 25, 2015
• Study Start: September 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: March 23, 2017

Record last verified: 2017-03