Abstract
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-associate...Continue Reading
References
Sep 20, 1991·Cell·T KitamuraA Miyajima
Sep 20, 1991·Cell·J TavernierG Plaetinck
Apr 3, 1999·Stroke; a Journal of Cerebral Circulation·S EbrahimG D Lowe
May 23, 2000·Diabetic Medicine : a Journal of the British Diabetic Association·B HedbladG Berglund
Feb 16, 2006·Lipids·William B Kannel
May 20, 2006·PLoS Genetics·Martin FarrallHugh Watkins
Mar 17, 2007·Platelets·G AvramakisE S Ganotakis
Sep 29, 2007·Stroke; a Journal of Cerebral Circulation·Stein Harald JohnsenEgil Arnesen
Oct 23, 2008·Journal of the American College of Cardiology·Maritta SämpiSohvi Hörkkö
Feb 10, 2009·Nature Genetics·Daniel F GudbjartssonKari Stefansson
Oct 13, 2009·International Immunology·Taku Kouro, Kiyoshi Takatsu
Dec 3, 2009·European Heart Journal·Damiano BaldassarreUNKNOWN IMPROVE study group
Mar 9, 2010·Current Opinion in Pharmacology·Soraya TalebZiad Mallat
Jun 22, 2010·Circulation. Cardiovascular Genetics·Lasse FolkersenUNKNOWN BiKE and ASAP study groups
Aug 14, 2010·JACC. Cardiovascular Imaging·Aloke V FinnRenu Virmani
Oct 4, 2011·PLoS Genetics·UNKNOWN IBC 50K CAD Consortium
Nov 8, 2011·Nature Genetics·Gosia TrynkaDavid A van Heel
Jan 17, 2012·The Journal of Allergy and Clinical Immunology·Erik IngelssonMagnus Bäck
Aug 10, 2012·PLoS Genetics·Benjamin F VoightMichael Boehnke
Sep 4, 2012·Nature Genetics·Elin GrundbergUNKNOWN Multiple Tissue Human Expression Resource (MuTHER) Consortium
Nov 16, 2012·Circulation. Cardiovascular Genetics·Karl GertowAnders Hamsten
Sep 10, 2013·Nature Genetics·Harm-Jan WestraLude Franke
Oct 1, 2013·Cell·Valeria OrrùFrancesco Cucca
Nov 29, 2013·Nucleic Acids Research·Liyuan GuoJing Wang
Feb 19, 2014·International Journal of Molecular Medicine·Salvatore Santo SignorelliGrazia Malaponte
Dec 23, 2014·Lancet·UNKNOWN GBD 2013 Mortality and Causes of Death Collaborators
Jan 15, 2015·Atherosclerosis·Angela SilveiraAnders Hamsten
Mar 17, 2015·Cell·Mario RoedererFrank O Nestle
Citations
Oct 21, 2016·Expert Review of Clinical Immunology·Meritxell Nus, Ziad Mallat
Feb 23, 2017·Allergy·S Prakash BabuA D Klion
Mar 4, 2020·Cell Biology International·Dan XianYingzhong Lin
Apr 20, 2018·Scientific Reports·Ling-Feng ZhaXiang Cheng
Oct 26, 2018·Circulation·Giampaolo NiccoliFilippo Crea
Apr 16, 2021·ERJ Open Research·Mathieu FieldesArnaud Bourdin
Aug 28, 2021·International Journal of Molecular Sciences·Anastasia V PoznyakAlexander N Orekhov