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Sökning: id:"swepub:oai:DiVA.org:uu-297283" > Genetic loci on chr...

  • McLeod, OlgaKarolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)

Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • Elsevier BV,2016
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-297283
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-297283URI
  • https://doi.org/10.1016/j.cyto.2016.01.007DOI
  • https://lup.lub.lu.se/record/8573046URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133429127URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding: The IMPROVE study was supported by the European Commission (LSHM-CT-2007-037273; Contract number: QLG1- CT- 2002-00896), the Swedish Heart-Lung Foundation, the Swedish Research Council (8311, 8691), the Knut and Alice Wallenberg Foundation, the Foundation for Strategic Research, the Torsten Soderbergs Stiftelse, the Strategic Cardiovascular Programme of Karolinska Institutet, the Stockholm County Council (560183) and Ministero della Salute Ricerca Corrente, Italy. PROCARDIS was supported by the British Heart Foundation, the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the Wellcome Trust, the United Kingdom Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Medical Research Council, the Knut and Alice Wallenberg Foundation, and the Karolinska Institutet. MDC was supported by Grants from the Swedish Research Council, the Swedish Heart-Lung foundation, the Knut and Alice Wallenberg Foundation, VINNOVA, Swedish Foundation for Strategic Research. KG acknowledges support from the Swedish Heart-Lung Foundation and Stiftelsen for Gamla Tjanarinnor. BS acknowledges support from the Magnus Bergvall Foundation and the Stiftelsen for Gamla Tjanarinnor. SEH is a British Heart Foundation Professor and is supported by the British Heart Foundation (RG008/08) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. JCH acknowledges support from the British Heart Foundation (FS/14/55/30806). RJS is supported by the SRP Diabetes Program at Karolinska Institutet.
  • IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E(-5) and chromosome 14, rs4902762, BETA = 0.12, P= 5.76E(-6)) and one for eosinophil count (rs72797327, BETA = -0.10, P = 1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P= 0.2763, I-2 = 24, I-2 - P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = -0.10, P = 8.64E(-6) and rs11739623 (r2 = 0.96 with rs72797327) BETA = -0.23, P = 1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNP5 associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Silveira, AngelaKarolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Valdes-Marquez, ElsaUniv Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England. (författare)
  • Björkbacka, HarryLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Lund Univ, Expt Cardiovasc Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.(Swepub:lu)medf-hbj (författare)
  • Almgren, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.(Swepub:lu)endo-pal (författare)
  • Gertow, KarlKarolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Gadin, Jesper R.Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Backlund, AlexandraKarolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Sennblad, BengtKarolinska Institutet,Karolinska Inst, Cardiovasc Med Unit, Dept Med, Sci Life Lab, S-17176 Stockholm, Sweden. (författare)
  • Baldassarre, DamianoUniv Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy. (författare)
  • Veglia, FabrizioIRCCS, Ctr Cardiol Monzino, Milan, Italy. (författare)
  • Humphries, Steve E.UCL, Ctr Cardiovasc Genet, London WC1E 6BT, England. (författare)
  • Tremoli, ElenaUniv Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy. (författare)
  • de Faire, UlfKarolinska Institutet,Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17176 Stockholm, Sweden. (författare)
  • Nilsson, JanLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Lund Univ, Expt Cardiovasc Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.(Swepub:lu)medf-jni (författare)
  • Melander, OlleLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Cardiovascular Research - Hypertension,Lund University Research Groups,Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.(Swepub:lu)endo-ome (författare)
  • Hopewell, Jemma C.Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England. (författare)
  • Clarke, RobertUniv Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England. (författare)
  • Bjorck, Hanna M.Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Hamsten, AndersKarolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Öhrvik, JohnUppsala universitet,Centrum för klinisk forskning, Västerås,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.(Swepub:uu)joohr789 (författare)
  • Strawbridge, Rona J.Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (författare)
  • Karolinska InstitutetKarolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Cytokine: Elsevier BV81, s. 1-91043-46661096-0023

Internetlänk

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  • Cytokine (Sök värdpublikationen i LIBRIS)

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