uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
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
Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
Lund Univ, Expt Cardiovasc Res Unit, Dept Clin Sci Malmo, Malmo, Sweden..
Show others and affiliations
2016 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 81, 1-9 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 81, 1-9 p.
Keyword [en]
Subclinical atherosclerosis, Intima-media thickness, Genetics, IL-5, Eosinophil count, RAD50
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-297283DOI: 10.1016/j.cyto.2016.01.007ISI: 000374802400001PubMedID: 26821299OAI: oai:DiVA.org:uu-297283DiVA: diva2:941600
Note

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.

Available from: 2016-06-22 Created: 2016-06-22 Last updated: 2016-06-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Centre for Clinical Research, County of Västmanland
In the same journal
Cytokine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 9 hits
ReferencesLink to record
Permanent link

Direct link