Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

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Sarwar, Nadeem (author)

Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies

Article/chapterEnglish2012

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New York, NY, USA :Elsevier,2012
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LIBRIS-ID:oai:DiVA.org:uu-173338
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-173338URI
https://doi.org/10.1016/S0140-6736(11)61931-4DOI
https://gup.ub.gu.se/publication/161399URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:124310123URI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54325URI
https://lup.lub.lu.se/record/2494682URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Allmänmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine General Practice hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Ortopedi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Orthopaedics hsv//eng

Added entries (persons, corporate bodies, meetings, titles ...)

Butterworth, Adam S. (author)
Freitag, Daniel F. (author)
Gregson, John (author)
Willeit, Peter (author)
Gorman, Donal N. (author)
Gao, Pei (author)
Saleheen, Danish (author)
Rendon, Augusto (author)
Nelson, Christopher P. (author)
Braund, Peter S. (author)
Hall, Alistair S. (author)
Chasman, Daniel I. (author)
Tybjaerg-Hansen, AnneKarolinska Institutet (author)
Chambers, John C. (author)
Benjamin, Emelia J. (author)
Franks, Paul W.Lunds universitet,Umeå universitet,Medicin,Lund University, Department of Clinical Science, Genetical & Molecular Epidemiology Unit, Malmö, Sweden and Harvard University, School of Public Health, Department of Nutrition, Boston, USA,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
Clarke, Robert (author)
Wilde, Arthur A. M. (author)
Trip, Mieke D. (author)
Steri, Maristella (author)
Witteman, Jacqueline C. M. (author)
Qi, Lu (author)
van der Schoot, C. Ellen (author)
de Faire, UlfKarolinska Institutet (author)
Erdmann, Jeanette (author)
Stringham, Heather M. (author)
Koenig, Wolfgang (author)
Rader, Daniel J. (author)
Melzer, David (author)
Reich, David (author)
Psaty, Bruce M. (author)
Kleber, Marcus E. (author)
Panagiotakos, Demosthenes B. (author)
Willeit, Johann (author)
Wennberg, Patrik (author)
Woodward, Mark (author)
Adamovic, Svetlana,1965Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xadasv (author)
Rimm, Eric B. (author)
Meade, Tom W. (author)
Gillum, Richard F. (author)
Shaffer, Jonathan A. (author)
Hofman, Albert (author)
Onat, Altan (author)
Sundström, JohanUppsala universitet,Institutionen för medicinska vetenskaper(Swepub:uu)johasund (author)
Wassertheil-Smoller, Sylvia (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Institute of Medicine, School of Public Health and Community Medicine(Swepub:gu)xmelda (author)
Gallacher, John (author)
Cushman, Mary (author)
Tracy, Russell P. (author)
Kauhanen, Jussi (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-mka (author)
Salonen, Jukka T. (author)
Wilhelmsen, Lars (author)
Amouyel, Philippe (author)
Cantin, Bernard (author)
Best, Lyle G. (author)
Ben-Shlomo, Yoav (author)
Manson, JoAnn E. (author)
Davey-Smith, George (author)
de Bakker, Paul I. W. (author)
Jansson, John-Olov,1954Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjanjo (author)
Wilson, James F. (author)
Wilson, Anthony G. (author)
Assimes, Themistocles L. (author)
Jansson, John-Olov (author)
Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
Tivesten, Åsa,1969Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xtivas (author)
Ljunggren, ÖstenUppsala universitet,Institutionen för medicinska vetenskaper,Metabola bensjukdomar(Swepub:uu)osteljun (author)
Reilly, Muredach P. (author)
Hamsten, Anders (author)
Ingelsson, ErikKarolinska Institutet (author)
Cambien, Francois (author)
Hung, Joseph (author)
Thomas, G. Neil (author)
Boehnke, Michael (author)
Schunkert, Heribert (author)
Asselbergs, Folkert W. (author)
Kastelein, John J. P. (author)
Gudnason, Vilmundur (author)
Salomaa, Veikko (author)
Harris, Tamara B. (author)
Kooner, Jaspal S. (author)
Allin, Kristine H. (author)
Nordestgaard, Borge G. (author)
Hopewell, Jemma C. (author)
Goodall, Alison H. (author)
Ridker, Paul M. (author)
Holm, Hilma (author)
Watkins, Hugh (author)
Ouwehand, Willem H. (author)
Samani, Nilesh J. (author)
Kaptoge, Stephen (author)
Di Angelantonio, Emanuele (author)
Harari, Olivier (author)
Danesh, John (author)
Karolinska InstitutetMedicin (creator_code:org_t)

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In:The LancetNew York, NY, USA : Elsevier379:9822, s. 1205-12130140-67361474-547X

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By the author/editor: Sarwar, Nadeem; Butterworth, Ada ...; Freitag, Daniel ...; Gregson, John; Willeit, Peter; Gorman, Donal N.; show more...; Gao, Pei; Saleheen, Danish; Rendon, Augusto; Nelson, Christop ...; Braund, Peter S.; Hall, Alistair S ...; Chasman, Daniel ...; Tybjaerg-Hansen, ...; Chambers, John C ...; Benjamin, Emelia ...; Franks, Paul W.; Clarke, Robert; Wilde, Arthur A. ...; Trip, Mieke D.; Steri, Maristell ...; Witteman, Jacque ...; Qi, Lu; van der Schoot, ...; de Faire, Ulf; Erdmann, Jeanett ...; Stringham, Heath ...; Koenig, Wolfgang; Rader, Daniel J.; Melzer, David; Reich, David; Psaty, Bruce M.; Kleber, Marcus E ...; Panagiotakos, De ...; Willeit, Johann; Wennberg, Patrik; Woodward, Mark; Adamovic, Svetla ...; Rimm, Eric B.; Meade, Tom W.; Gillum, Richard ...; Shaffer, Jonatha ...; Hofman, Albert; Onat, Altan; Sundström, Johan; Wassertheil-Smol ...; Mellström, Dan, ...; Gallacher, John; Cushman, Mary; Tracy, Russell P ...; Kauhanen, Jussi; Karlsson, Magnus; Salonen, Jukka T ...; Wilhelmsen, Lars; Amouyel, Philipp ...; Cantin, Bernard; Best, Lyle G.; Ben-Shlomo, Yoav; Manson, JoAnn E.; Davey-Smith, Geo ...; de Bakker, Paul ...; Jansson, John-Ol ...; Wilson, James F.; Wilson, Anthony ...; Assimes, Themist ...; Jansson, John-Ol ...; Ohlsson, Claes, ...; Tivesten, Åsa, 1 ...; Ljunggren, Östen; Reilly, Muredach ...; Hamsten, Anders; Ingelsson, Erik; Cambien, Francoi ...; Hung, Joseph; Thomas, G. Neil; Boehnke, Michael; Schunkert, Herib ...; Asselbergs, Folk ...; Kastelein, John ...; Gudnason, Vilmun ...; Salomaa, Veikko; Harris, Tamara B ...; Kooner, Jaspal S ...; Allin, Kristine ...; Nordestgaard, Bo ...; Hopewell, Jemma ...; Goodall, Alison ...; Ridker, Paul M.; Holm, Hilma; Watkins, Hugh; Ouwehand, Willem ...; Samani, Nilesh J ...; Kaptoge, Stephen; Di Angelantonio, ...; Harari, Olivier; Danesh, John; show less...

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