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Sökning: WFRF:(Tragante Vinicius) > (2020-2024) > Genetically determi...

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FältnamnIndikatorerMetadata
00016354naa a2201321 4500
001oai:DiVA.org:uu-448804
003SwePub
008210709s2021 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:62a33c65-b1a0-4cef-a193-463b0e13dd9d
024a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4488042 URI
024a https://doi.org/10.1093/eurheartj/ehab1072 DOI
024a https://lup.lub.lu.se/record/62a33c65-b1a0-4cef-a193-463b0e13dd9d2 URI
040 a (SwePub)uud (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Schunk, Stefan J.u Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany,Saarland University Hospital4 aut
2451 0a Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
264 c 2021-03-22
264 1b Oxford University Press,c 2021
338 a print2 rdacarrier
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
653 a Cardiovascular diseases
653 a Coronary artery disease
653 a Inflammation
653 a Inflammasome
653 a NLRP3
653 a Cardiovascular diseases
653 a Coronary artery disease
653 a Inflammasome
653 a Inflammation
653 a NLRP3
700a Kleber, Marcus E.u 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, Germany4 aut
700a März, Winfriedu 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, Germany4 aut
700a Pang, Shichaou Tech Univ Munich, Deutsch Herzzentrum Munchen, Kardiol, Lazarettstr 36, D-80636 Munich, Germany4 aut
700a Zewinger, Stephenu Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany4 aut
700a Triem, Sarahu Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany4 aut
700a Ege, Philippu Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany4 aut
700a Reichert, Matthias C.u Saarland Univ, Dept Med 2, Med Ctr, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Krawczyk, Marcinu 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, Poland4 aut
700a Weber, Susanne N.u Saarland Univ, Dept Med 2, Med Ctr, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Jaumann, Isabellau Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany4 aut
700a Schmit, Davidu Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany4 aut
700a Sarakpi, Tamimu Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str, Bldg 41, D-66424 Homburg, Germany4 aut
700a Wagenpfeil, Stefanu Saarland Univ, Inst Med Biometry Epidemiol & Med Informat, Campus Homburg Saar, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Kramann, Rafaelu 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, Germany4 aut
700a Boerwinkle, Ericu 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 USA4 aut
700a Ballantyne, Christie M.u 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 USA4 aut
700a Grove, Megan L.u Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Human Genet Ctr, 1200 Pressler St, Houston, TX 77030 USA4 aut
700a Tragante, Viniciusu UMC Utrecht, Heart & Lungs Div, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands4 aut
700a Pilbrow, Anna P.u Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand4 aut
700a Richards, A. Marku Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand4 aut
700a Cameron, Vicky A.u Univ Otago Christchurch, Christchurch Heart Inst, 2 Riccarton Ave, Christchurch 8011, New Zealand4 aut
700a Doughty, Robert N.u Univ Auckland, Heart Hlth Res Grp, Level 2, 22-30 Pk Ave, Auckland, New Zealand4 aut
700a Dubé, Marie-Pierreu 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, Canada4 aut
700a Tardif, Jean-Claudeu 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, Canada4 aut
700a Feroz-Zada, Yassaminu Montreal Heart Inst, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada4 aut
700a Sun, Maxineu Univ Montreal, Fac Med, Pavillon Roger Gaudry,2900 Edouard Montpetit Blvd, Montreal, PQ H3T 1J4, Canada4 aut
700a Liu, Changu Emory Univ, Emory Clin Cardiovasc Res Inst, Div Cardiol, Sch Med, 1462 Clifton Rd NE, Atlanta, GA 30322 USA4 aut
700a Ko, Yi-Anu Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, 1518 Clifton Rd NE, Atlanta, GA 30322 USA4 aut
700a Quyyumi, Arshed A.u Emory Univ, Emory Clin Cardiovasc Res Inst, Div Cardiol, Sch Med, 1462 Clifton Rd NE, Atlanta, GA 30322 USA4 aut
700a Hartiala, Jaana A.u Univ Southern Calif, Keck Sch Med, Dept Prevent Med, 2001 N Soto St, Los Angeles, CA 90033 USA4 aut
700a Tang, W. H. Wilsonu 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 Zealand4 aut
700a Hazen, Stanley L.u 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 USA4 aut
700a Allayee, Hoomanu Univ Southern Calif, Keck Sch Med, Dept Prevent Med, 2001 N Soto St, Los Angeles, CA 90033 USA4 aut
700a McDonough, Caitrin W.u Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA4 aut
700a Gong, Yanu Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1225 Ctr Dr, HPNP Bldg, Gainesville, FL 32610 USA4 aut
700a Cooper-DeHoff, Rhonda M.u 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 USA4 aut
700a Johnson, Julie A.u 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 USA4 aut
700a Scholz, Markusu 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, Germany4 aut
700a Teren, Andreju Univ Leipzig, LIFE Res Ctr Civilizat Dis, Hartelstr 16-18, D-04107 Leipzig, Germany; Heart Ctr Leipzig, Strumpellstr 39, D-04289 Leipzig, Germany4 aut
700a Burkhardt, Ralphu 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, Germany4 aut
700a Martinsson, Andreasu Sahlgrens Univ Hosp, Dept Cardiol, Blå Stråket 5, S-41345 Gothenburg, Sweden4 aut
700a Smith, J. Gustavu 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, Sweden4 aut0 (Swepub:lu)med-gvs
700a Wallentin, Lars,d 1943-u Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)larswall
700a James, Stefan K.,d 1964-u Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)4 aut0 (Swepub:uu)stjam367
700a Eriksson, Niclas,d 1978-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi4 aut0 (Swepub:uu)nieri103
700a White, Harveyu Auckland City Hosp, Green Lane Cardiovasc Serv, 2 Pk Rd, Auckland 1023, New Zealand4 aut
700a Held, Claes,d 1956-u Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi4 aut0 (Swepub:uu)clahe947
700a Waterworth, Dawnu GlaxoSmithKline, Genet, 709 Swedeland Rd, King Of Prussia, PA 19406 USA4 aut
700a Trompet, Stellau Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands4 aut
700a Jukema, J. Wouteru 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, Germany4 aut
700a Ford, Ianu Univ Glasgow, Robertson Ctr Biostat, Boyd Orr Bldg, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland4 aut
700a Stott, David J.u Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland4 aut
700a Sattar, Naveedu Univ Glasgow, BHF Glasgow Res Ctr, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland4 aut
700a Cresci, Sharonu 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 USA4 aut
700a Spertus, John A.u st Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.;Univ Missouri, 4401 Wornall Rd, Kansas City, MO 64111 USA4 aut
700a Campbell, Hannahu 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 USA4 aut
700a Tierling, Saschau Saarland Univ, Fac Nat Sci & Technol, Dept Genet Epigenet, Postfach 151150, D-66041 Saarbrucken, Germany4 aut
700a Walter, Jörnu Saarland Univ, Fac Nat Sci & Technol, Dept Genet Epigenet, Postfach 151150, D-66041 Saarbrucken, Germany4 aut
700a Ampofo, Emmanuelu Saarland Univ, Inst Clin & Expt Surg, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Niemeyer, Barbara A.u Saarland Univ, CIPMM, Mol Biophys, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Lipp, Peteru Saarland Univ, Med Fac, Ctr Mol Signaling PZMS, Res Ctr Mol Imaging & Screening, Kirrberger Str, D-66424 Homburg, Germany4 aut
700a Schunkert, Heribertu 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, Germany4 aut
700a Böhm, Michaelu Saarland Univ Hosp, Dept Internal Med Cardiol Angiol & Intens Care Me, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany4 aut
700a Koenig, Wolfgangu 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, Germany4 aut
700a Fliser, Danilou Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germany4 aut
700a Laufs, Ulrichu Univ Med Ctr Leipzig, Dept Cardiol, Liebigstr 20, Leipzig, Germany4 aut
700a Speer, Thimoteusu 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 Hospital4 aut
710a Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens 4, Kirrberger Str,Bldg 41, D-66424 Homburg, Germanyb Saarland University Hospital4 org
710a eQTLGen consortium
710a BIOS consortium
773t European Heart Journald : Oxford University Pressg 42:18, s. 1742-1756q 42:18<1742-1756x 0195-668Xx 1522-9645
856u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85106539003&doi=10.1093%2feurheartj%2fehab107&partnerID=40&md5=62dd2fde089cce4a5c8b922dab9933b3y FULLTEXT
856u http://dx.doi.org/10.1093/eurheartj/ehab107y FULLTEXT
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-448804
8564 8u https://doi.org/10.1093/eurheartj/ehab107
8564 8u https://lup.lub.lu.se/record/62a33c65-b1a0-4cef-a193-463b0e13dd9d

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Reichert, Matthi ...
Krawczyk, Marcin
Weber, Susanne N ...
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Schmit, David
Sarakpi, Tamim
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Kramann, Rafael
Boerwinkle, Eric
Ballantyne, Chri ...
Grove, Megan L.
Tragante, Vinici ...
Pilbrow, Anna P.
Richards, A. Mar ...
Cameron, Vicky A ...
Doughty, Robert ...
Dubé, Marie-Pier ...
Tardif, Jean-Cla ...
Feroz-Zada, Yass ...
Sun, Maxine
Liu, Chang
Ko, Yi-An
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Hartiala, Jaana ...
Tang, W. H. Wils ...
Hazen, Stanley L ...
Allayee, Hooman
McDonough, Caitr ...
Gong, Yan
Cooper-DeHoff, R ...
Johnson, Julie A ...
Scholz, Markus
Teren, Andrej
Burkhardt, Ralph
Martinsson, Andr ...
Smith, J. Gustav
Wallentin, Lars, ...
James, Stefan K. ...
Eriksson, Niclas ...
White, Harvey
Held, Claes, 195 ...
Waterworth, Dawn
Trompet, Stella
Jukema, J. Woute ...
Ford, Ian
Stott, David J.
Sattar, Naveed
Cresci, Sharon
Spertus, John A.
Campbell, Hannah
Tierling, Sascha
Walter, Jörn
Ampofo, Emmanuel
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Schunkert, Herib ...
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