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

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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

McLeod, Olga (author): Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Silveira, Angela (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Valdes-Marquez, Elsa (author): Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England.

Björkbacka, Harry (author): Lund 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.

Almgren, Peter (author): Lund 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.

Gertow, Karl (author): Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Gadin, Jesper R. (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Backlund, Alexandra (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Sennblad, Bengt (author): Karolinska Institutet,Karolinska Inst, Cardiovasc Med Unit, Dept Med, Sci Life Lab, S-17176 Stockholm, Sweden.

Baldassarre, Damiano (author): Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy.

Veglia, Fabrizio (author): IRCCS, Ctr Cardiol Monzino, Milan, Italy.

Humphries, Steve E. (author): UCL, Ctr Cardiovasc Genet, London WC1E 6BT, England.

Tremoli, Elena (author): Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy.

de Faire, Ulf (author): Karolinska Institutet,Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17176 Stockholm, Sweden.

Nilsson, Jan (author): Lund 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.

Melander, Olle (author): Lund 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.

Hopewell, Jemma C. (author): Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England.

Clarke, Robert (author): Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England.

Bjorck, Hanna M. (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Hamsten, Anders (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Öhrvik, John (author): Uppsala universitet,Centrum för klinisk forskning, Västerås,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

Strawbridge, Rona J. (author): Karolinska Institutet,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden.

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Karolinska Institutet Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden (creator_code:org_t)

Elsevier BV, 2016
2016
English.
In: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 81, s. 1-9

Related links:: https://doi.org/10.1...; show more...; https://doi.org/10.1...; http://www.ncbi.nlm....; http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

Articles in the publication: Cytokine

By the university: Uppsala University; Lund University; Karolinska Institutet

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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

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