@article{16339,
  author = {Gao P. and Psaty B. and Asselbergs F. and Sarwar N. and Butterworth A. and Freitag D. and Gregson J. and Willeit P. and Gorman D. and Saleheen D. and Rendon A. and Nelson C. and Braund P. and Hall A. and Chasman D. and Tybjaerg-Hansen A. and Chambers J. and Benjamin E. and Franks P. and Clarke R. and Wilde A. and Trip M. and Steri M. and Witteman J. and Qi L. and van der Schoot C. and de Faire U. and Erdmann J. and Stringham H. and Koenig W. and Rader D. and Melzer D. and Reich D. and Kleber M. and Panagiotakos D. and Willeit J. and Wennberg P. and Adamovic S. and Rimm E. and Meade T. and Gillum R. and Shaffer J. and Hofman A. and Onat A. and Sundstrom J. and Wassertheil-Smoller S. and Mellstrom D. and Gallacher J. and Cushman M. and Tracy R. and Kauhanen J. and Karlsson M. and Salonen J. and Wilhelmsen L. and Amouyel P. and Cantin B. and Best L. and Ben-Shlomo Y. and Manson J. and Davey-Smith G. and de Bakker P. and O'Donnell C. and Wilson J. and Wilson A. and Assimes T. and Jansson J. and Ohlsson C. and Tivesten A. and Ljunggren O. and Reilly M. and Hamsten A. and Ingelsson E. and Hung J. and Thomas G. and Boehnke M. and Schunkert H. and Kastelein J. and Gudnason V. and Salomaa V. and Harris T. and Kooner J. and Allin K. and Nordestgaard B. and Hopewell J. and Goodall A. and Ridker P. and Holm H. and Watkins H. and Ouwehand W. and Samani N. and Kaptoge S. and Di Angelantonio E. and Harari O. and Danesh J. and Woodward Mark and IL6R Genetics Consortium Emerging Risk Factors Collaboration and Cambien F.},
  title = {Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies},
  abstract = {<p>
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 &gt;/=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. FUNDING: British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.
</p>
},
  year = {2012},
  journal = {Lancet},
  volume = {379},
  edition = {2012/03/17},
  number = {9822},
  pages = {1205-13},
  month = {204106444252},
  isbn = {1474-547X (Electronic)0140-6736 (Linking)},
  note = {IL6R Genetics Consortium Emerging Risk Factors CollaborationSarwar, NadeemButterworth, Adam SFreitag, Daniel FGregson, JohnWilleit, PeterGorman, Donal NGao, PeiSaleheen, DanishRendon, AugustoNelson, Christopher PBraund, Peter SHall, Alistair SChasman, Daniel ITybjaerg-Hansen, AnneChambers, John CBenjamin, Emelia JFranks, Paul WClarke, RobertWilde, Arthur A MTrip, Mieke DSteri, MaristellaWitteman, Jacqueline C MQi, Luvan der Schoot, C Ellende Faire, UlfErdmann, JeanetteStringham, Heather MKoenig, WolfgangRader, Daniel JMelzer, DavidReich, DavidPsaty, Bruce MKleber, Marcus EPanagiotakos, Demosthenes BWilleit, JohannWennberg, PatrikWoodward, MarkAdamovic, SvetlanaRimm, Eric BMeade, Tom WGillum, Richard FShaffer, Jonathan AHofman, AlbertOnat, AltanSundstrom, JohanWassertheil-Smoller, SylviaMellstrom, DanGallacher, JohnCushman, MaryTracy, Russell PKauhanen, JussiKarlsson, MagnusSalonen, Jukka TWilhelmsen, LarsAmouyel, PhilippeCantin, BernardBest, Lyle GBen-Shlomo, YoavManson, JoAnn EDavey-Smith, Georgede Bakker, Paul I WO'Donnell, Christopher JWilson, James FWilson, Anthony GAssimes, Themistocles LJansson, John-OlovOhlsson, ClaesTivesten, AsaLjunggren, OstenReilly, Muredach PHamsten, AndersIngelsson, ErikCambien, FrancoisHung, JosephThomas, G NeilBoehnke, MichaelSchunkert, HeribertAsselbergs, Folkert WKastelein, John J PGudnason, VilmundurSalomaa, VeikkoHarris, Tamara BKooner, Jaspal SAllin, Kristine HNordestgaard, Borge GHopewell, Jemma CGoodall, Alison HRidker, Paul MHolm, HilmaWatkins, HughOuwehand, Willem HSamani, Nilesh JKaptoge, StephenDi Angelantonio, EmanueleHarari, OlivierDanesh, JohnRG/08/014/British Heart Foundation/United KingdomMedical Research Council/United KingdomMeta-AnalysisResearch Support, Non-U.S. Gov'tEnglandLancet. 2012 Mar 31;379(9822):1205-13. Epub 2012 Mar 14.},
  language = {eng},
}