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Genetically determi...
Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
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- Schunk, Stefan J. (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany,Saarland University Hospital
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- Kleber, Marcus E. (författare)
- Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany; SYNLAB MVZ Humangenet Mannheim, Harrlachweg 1, D-68163 Mannheim, Germany
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- März, Winfried (författare)
- Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany; Med Univ Graz, Clin Inst Med & Lab Diagnost, Auenbruggerpl 2, A-8036 Graz, Austria; Synlab Holding GmbH, Synlab Acad, Harrlachweg 1, D-68163 Mannheim, Germany
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visa fler...
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- Pang, Shichao (författare)
- Tech Univ Munich, Deutsch Herzzentrum Munchen, Kardiol, Lazarettstr 36, D-80636 Munich, Germany
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- Zewinger, Stephen (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany
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- Triem, Sarah (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany
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- Ege, Philipp (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany
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- Reichert, Matthias C. (författare)
- Saarland Univ, Dept Med 2, Med Ctr, Kirrberger Str, D-66424 Homburg, Germany
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- Krawczyk, Marcin (författare)
- Saarland Univ, Dept Med 2, Med Ctr, Kirrberger Str, D-66424 Homburg, Germany; Med Univ Warsaw, Ctr Preclin Res, Dept Gen Transplant & Liver Surg, Lab Metab Liver Dis, CePT, Ul Banacha 1B, PL-02097 Warsaw, Poland
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- Weber, Susanne N. (författare)
- Saarland Univ, Dept Med 2, Med Ctr, Kirrberger Str, D-66424 Homburg, Germany
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- Jaumann, Isabella (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany
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- Schmit, David (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany
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- Sarakpi, Tamim (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany
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- Wagenpfeil, Stefan (författare)
- Saarland Univ, Inst Med Biometry Epidemiol & Med Informat, Campus Homburg Saar, Kirrberger Str, D-66424 Homburg, Germany
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- Kramann, Rafael (författare)
- Rhein Westfal TH Aachen, Div Nephrol & Clin Immunol, Pauwelsstr 30, D-52074 Aachen, Germany; Rhein Westfal TH Aachen, Inst Expt Med & Syst Biol, Pauwelsstr 30, D-52074 Aachen, Germany
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- Boerwinkle, Eric (författare)
- Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Human Genet Ctr, 1200 Pressler St, Houston, TX 77030 USA; Baylor Coll Med, Human Genome Sequencing Ctr, BCM226, Houston, TX 77030 USA
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- Ballantyne, Christie M. (författare)
- Baylor Coll Med, Dept Med, Sect Cardiovasc Res, One Baylor Plaza, Houston, TX 77030 USA; Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, 6565 Fannin St, Houston, TX 77030 USA
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- Grove, Megan L. (författare)
- Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Human Genet Ctr, 1200 Pressler St, Houston, TX 77030 USA
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- Tragante, Vinicius (författare)
- UMC Utrecht, Heart & Lungs Div, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands
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- Pilbrow, Anna P. (författare)
- Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand
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- Richards, A. Mark (författare)
- Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand
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- Cameron, Vicky A. (författare)
- Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand
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- Doughty, Robert N. (författare)
- Univ Auckland, Heart Hlth Res Grp, Level 2, 22-30 Pk Ave, Auckland, New Zealand
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- Dubé, Marie-Pierre (författare)
- Montreal Heart Inst, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada; Univ Montreal, Fac Med, Pavillon Roger Gaudry, 2900 Edouard Montpetit Blvd, Montreal, PQ H3T 1J4, Canada
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- Tardif, Jean-Claude (författare)
- Montreal Heart Inst, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada; Univ Montreal, Fac Med, Pavillon Roger Gaudry,2900 Edouard Montpetit Blvd, Montreal, PQ H3T 1J4, Canada
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- Feroz-Zada, Yassamin (författare)
- Montreal Heart Inst, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada
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- Sun, Maxine (författare)
- Univ Montreal, Fac Med, Pavillon Roger Gaudry,2900 Edouard Montpetit Blvd, Montreal, PQ H3T 1J4, Canada
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- Liu, Chang (författare)
- Emory Univ, Emory Clin Cardiovasc Res Inst, Div Cardiol, Sch Med, 1462 Clifton Rd NE, Atlanta, GA 30322 USA
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- Ko, Yi-An (författare)
- Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, 1518 Clifton Rd NE, Atlanta, GA 30322 USA
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- Quyyumi, Arshed A. (författare)
- Emory Univ, Emory Clin Cardiovasc Res Inst, Div Cardiol, Sch Med, 1462 Clifton Rd NE, Atlanta, GA 30322 USA
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- Hartiala, Jaana A. (författare)
- Univ Southern Calif, Keck Sch Med, Dept Prevent Med, 2001 N Soto St, Los Angeles, CA 90033 USA
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- Tang, W. H. Wilson (författare)
- Cleveland Clin, Dept Cardiovasc Med, 9500 Euclid Ave, Cleveland, OH 44195 USA; Cleveland Clin, Dept Cardiovasc & Metab Sci, Lerner Res Inst, 9500 Euclid Ave, NB 21, Cleveland, OH 44195 USA,Auckland City Hosp, Green Lane Cardiovasc Serv, 2 Pk Rd, Auckland 1023, New Zealand
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- Hazen, Stanley L. (författare)
- Cleveland Clin, Dept Cardiovasc Med, 9500 Euclid Ave, Cleveland, OH 44195 USA; Cleveland Clin, Dept Cardiovasc & Metab Sci, Lerner Res Inst, 9500 Euclid Ave, NB 21, Cleveland, OH 44195 USA
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- Allayee, Hooman (författare)
- Univ Southern Calif, Keck Sch Med, Dept Prevent Med, 2001 N Soto St, Los Angeles, CA 90033 USA
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- McDonough, Caitrin W. (författare)
- Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA
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- Gong, Yan (författare)
- Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA
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- Cooper-DeHoff, Rhonda M. (författare)
- Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA; Univ Florida, Dept Med, Div Cardiovasc Med, 1600 SW Archer Rd, Gainesville, FL 32610 USA
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- Johnson, Julie A. (författare)
- Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA; Univ Florida, Dept Med, Div Cardiovasc Med, 1600 SW Archer Rd, Gainesville, FL 32610 USA
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- Scholz, Markus (författare)
- Univ Leipzig, Inst Med Informat Stat & Epidemiol, Hartelstr 16-18, D-04107 Leipzig, Germany; Univ Leipzig, LIFE Res Ctr Civilizat Dis, Hartelstr 16-18, D-04107 Leipzig, Germany
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- Teren, Andrej (författare)
- Univ Leipzig, LIFE Res Ctr Civilizat Dis, Hartelstr 16-18, D-04107 Leipzig, Germany; Heart Ctr Leipzig, Strumpellstr 39, D-04289 Leipzig, Germany
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- Burkhardt, Ralph (författare)
- Univ Leipzig, LIFE Res Ctr Civilizat Dis, Hartelstr 16-18, D-04107 Leipzig, Germany; Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany
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- Martinsson, Andreas (författare)
- Sahlgrens Univ Hosp, Dept Cardiol, Blå Stråket 5, S-41345 Gothenburg, Sweden
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- Smith, J. Gustav (författare)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,Lund Univ, Dept Cardiol, Clin Sci, BMC F12, S-22184 Lund, Sweden; Skåne Univ Hosp, BMC F12, S-22184 Lund, Sweden
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- Wallentin, Lars, 1943- (författare)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
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- James, Stefan K., 1964- (författare)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
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- Eriksson, Niclas, 1978- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- White, Harvey (författare)
- Auckland City Hosp, Green Lane Cardiovasc Serv, 2 Pk Rd, Auckland 1023, New Zealand
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- Held, Claes, 1956- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Waterworth, Dawn (författare)
- GlaxoSmithKline, Genet, 709 Swedeland Rd, King Of Prussia, PA 19406 USA
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- Trompet, Stella (författare)
- Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands
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- Jukema, J. Wouter (författare)
- Leiden Univ, Dept Cardiol, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands; Netherlands Heart Inst, Moreelsepk 1, NL-3511 EP Utrecht, Netherlands,Saarland Univ, Fac Nat Sci & Technol, Dept Genet Epigenet, Postfach 151150, D-66041 Saarbrucken, Germany
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- Ford, Ian (författare)
- Univ Glasgow, Robertson Ctr Biostat, Boyd Orr Bldg, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland
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- Stott, David J. (författare)
- Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland
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- Sattar, Naveed (författare)
- Univ Glasgow, BHF Glasgow Res Ctr, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland
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- Cresci, Sharon (författare)
- Washington Univ, Sch Med, 2300 I St NW, Washington, DC 20052 USA; Dept Med & Genet, Campus Box 8232, 4515 McKinley Ave, St Louis, MO 63110 USA
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- Spertus, John A. (författare)
- st Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.;Univ Missouri, 4401 Wornall Rd, Kansas City, MO 64111 USA
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- Campbell, Hannah (författare)
- Washington Univ, Sch Med, 2300 I St NW, Washington, DC 20052 USA; Dept Med & Genet, Campus Box 8232, 4515 McKinley Ave, St Louis, MO 63110 USA
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- Tierling, Sascha (författare)
- Saarland Univ, Fac Nat Sci & Technol, Dept Genet Epigenet, Postfach 151150, D-66041 Saarbrucken, Germany
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- Walter, Jörn (författare)
- Saarland Univ, Fac Nat Sci & Technol, Dept Genet Epigenet, Postfach 151150, D-66041 Saarbrucken, Germany
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- Ampofo, Emmanuel (författare)
- Saarland Univ, Inst Clin & Expt Surg, Kirrberger Str, D-66424 Homburg, Germany
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- Niemeyer, Barbara A. (författare)
- Saarland Univ, CIPMM, Mol Biophys, Kirrberger Str, D-66424 Homburg, Germany
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- Lipp, Peter (författare)
- Saarland Univ, Med Fac, Ctr Mol Signaling PZMS, Res Ctr Mol Imaging & Screening, Kirrberger Str, D-66424 Homburg, Germany
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- Schunkert, Heribert (författare)
- Tech Univ Munich, Deutsch Herzzentrum Munchen, Kardiol, Lazarettstr 36, D-80636 Munich, Germany; German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Ismaninger Str 22, D-81675 Munich, Germany
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- Böhm, Michael (författare)
- Saarland Univ Hosp, Dept Internal Med Cardiol Angiol & Intens Care Me, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany
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- Koenig, Wolfgang (författare)
- Tech Univ Munich, Deutsch Herzzentrum Munchen, Kardiol, Lazarettstr 36, D-80636 Munich, Germany; German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Ismaninger Str 22, D-81675 Munich, Germany; Univ Ulm, Inst Epidemiol & Med Biometry, Helmholtzstr 22, D-89081 Ulm, Germany
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- Fliser, Danilo (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany
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- Laufs, Ulrich (författare)
- Univ Med Ctr Leipzig, Dept Cardiol, Liebigstr 20, Leipzig, Germany
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- Speer, Thimoteus (författare)
- Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany; Saarland Univ, Translat Cardiorenal Med, Kirrberger Str, D-66424 Homburg, Germany,Saarland University Hospital
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- 2021-03-22
- 2021
- Engelska.
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
- Relaterad länk:
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https://www.scopus.c...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Cardiovascular diseases
- Coronary artery disease
- Inflammation
- Inflammasome
- NLRP3
- Cardiovascular diseases
- Coronary artery disease
- Inflammasome
- Inflammation
- NLRP3
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Schunk, Stefan J ...
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Kleber, Marcus E ...
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März, Winfried
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Pang, Shichao
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Zewinger, Stephe ...
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Triem, Sarah
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visa fler...
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Ege, Philipp
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Reichert, Matthi ...
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Krawczyk, Marcin
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Weber, Susanne N ...
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Jaumann, Isabell ...
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Schmit, David
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Sarakpi, Tamim
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Wagenpfeil, Stef ...
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Kramann, Rafael
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Boerwinkle, Eric
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Ballantyne, Chri ...
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Grove, Megan L.
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Tragante, Vinici ...
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Pilbrow, Anna P.
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Richards, A. Mar ...
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Cameron, Vicky A ...
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Doughty, Robert ...
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Dubé, Marie-Pier ...
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Tardif, Jean-Cla ...
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Feroz-Zada, Yass ...
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Sun, Maxine
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Liu, Chang
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Ko, Yi-An
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Quyyumi, Arshed ...
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Hartiala, Jaana ...
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Tang, W. H. Wils ...
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Hazen, Stanley L ...
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Allayee, Hooman
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McDonough, Caitr ...
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Gong, Yan
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Cooper-DeHoff, R ...
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Johnson, Julie A ...
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Scholz, Markus
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Teren, Andrej
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Burkhardt, Ralph
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Martinsson, Andr ...
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Smith, J. Gustav
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Wallentin, Lars, ...
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James, Stefan K. ...
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Eriksson, Niclas ...
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White, Harvey
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Held, Claes, 195 ...
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Waterworth, Dawn
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Trompet, Stella
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Jukema, J. Woute ...
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Ford, Ian
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Stott, David J.
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Sattar, Naveed
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Cresci, Sharon
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Spertus, John A.
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Campbell, Hannah
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Tierling, Sascha
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Walter, Jörn
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Ampofo, Emmanuel
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Niemeyer, Barbar ...
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Lipp, Peter
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Schunkert, Herib ...
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Böhm, Michael
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Koenig, Wolfgang
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Fliser, Danilo
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Laufs, Ulrich
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Speer, Thimoteus
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk geneti ...
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European Heart J ...
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