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; Silveira, Angela; Valdes-Marquez, Elsa; Björkbacka, Harry; Almgren, Peter; Gertow, Karl; Gådin, Jesper R; Bäcklund, Alexandra; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Nilsson, Jan; Melander, Olle; Hopewell, Jemma C; Clarke, Robert; Björck, Hanna M; Hamsten, Anders; Öhrvik, John; Strawbridge, Rona J.

I: Cytokine, Vol. 81, 2016, s. 1-9.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

McLeod, O, Silveira, A, Valdes-Marquez, E, Björkbacka, H, Almgren, P, Gertow, K, Gådin, JR, Bäcklund, A, Sennblad, B, Baldassarre, D, Veglia, F, Humphries, SE, Tremoli, E, de Faire, U, Nilsson, J, Melander, O, Hopewell, JC, Clarke, R, Björck, HM, Hamsten, A, Öhrvik, J & Strawbridge, RJ 2016, '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.', Cytokine, vol. 81, s. 1-9. https://doi.org/10.1016/j.cyto.2016.01.007

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CBE

McLeod O, Silveira A, Valdes-Marquez E, Björkbacka H, Almgren P, Gertow K, Gådin JR, Bäcklund A, Sennblad B, Baldassarre D, Veglia F, Humphries SE, Tremoli E, de Faire U, Nilsson J, Melander O, Hopewell JC, Clarke R, Björck HM, Hamsten A, Öhrvik J, Strawbridge RJ. 2016. 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. Cytokine. 81:1-9. https://doi.org/10.1016/j.cyto.2016.01.007

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McLeod, Olga ; Silveira, Angela ; Valdes-Marquez, Elsa ; Björkbacka, Harry ; Almgren, Peter ; Gertow, Karl ; Gådin, Jesper R ; Bäcklund, Alexandra ; Sennblad, Bengt ; Baldassarre, Damiano ; Veglia, Fabrizio ; Humphries, Steve E ; Tremoli, Elena ; de Faire, Ulf ; Nilsson, Jan ; Melander, Olle ; Hopewell, Jemma C ; Clarke, Robert ; Björck, Hanna M ; Hamsten, Anders ; Öhrvik, John ; Strawbridge, Rona J. / 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. I: Cytokine. 2016 ; Vol. 81. s. 1-9.

RIS

TY - JOUR

T1 - 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.

AU - McLeod, Olga

AU - Silveira, Angela

AU - Valdes-Marquez, Elsa

AU - Björkbacka, Harry

AU - Almgren, Peter

AU - Gertow, Karl

AU - Gådin, Jesper R

AU - Bäcklund, Alexandra

AU - Sennblad, Bengt

AU - Baldassarre, Damiano

AU - Veglia, Fabrizio

AU - Humphries, Steve E

AU - Tremoli, Elena

AU - de Faire, Ulf

AU - Nilsson, Jan

AU - Melander, Olle

AU - Hopewell, Jemma C

AU - Clarke, Robert

AU - Björck, Hanna M

AU - Hamsten, Anders

AU - Öhrvik, John

AU - Strawbridge, Rona J

PY - 2016

Y1 - 2016

N2 - 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 SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

AB - 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 SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

U2 - 10.1016/j.cyto.2016.01.007

DO - 10.1016/j.cyto.2016.01.007

M3 - Article

VL - 81

SP - 1

EP - 9

JO - Cytokine

T2 - Cytokine

JF - Cytokine

SN - 1096-0023

ER -