ArticleDiabetes2014
Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits.
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Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% of its field
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
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- An epigenome-wide association study of metabolic syndrome and its components.Scientific reports · 2020Article
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- Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.Nature reviews. Cardiology · 2018Review
- IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin-1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Attenuation of high sucrose diet-induced insulin resistance in ABC transporter deficientIntegrative obesity and diabetes · 2016Article
- Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts.Diabetes · 2016Article
- Review
- Appetitive traits as behavioural pathways in genetic susceptibility to obesity: a population-based cross-sectional study.Scientific reports · 2015Article
- Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis.The lancet. Diabetes & endocrinology · 2015Article
- Closing the gap between knowledge and clinical application: challenges for genomic translation.PLoS genetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 20 institutions in 7 countries.
Christian HerderInstitute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Germany christian.herder@ddz.uni-duesseldorf.de.
Marja-Liisa NuotioInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland Unit of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland.
Sonia ShahCentre of Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, St. Lucia, QLD, Australia.
Stefan BlankenbergClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
Eric J BrunnerDepartment of Epidemiology and Public Health, University College London, London, U.K.
Maren CarstensenInstitute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Germany.
Christian GiegerInstitute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Harald GrallertResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany German Center for Diabetes Research (DZD e.V.), partner site, Munich, Germany.
Antti JulaNational Institute for Health and Welfare, Turku, Finland.
Mika KähönenDepartment of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Johannes KettunenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland Unit of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland Computational Medicine, Institute of Health Sciences, University of Oulu and Oulu University Hospital, Oulu, Finland.
Mika KivimäkiDepartment of Epidemiology and Public Health, University College London, London, U.K.
Wolfgang KoenigDepartment of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
Kati KristianssonUnit of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland.
Claudia LangenbergDepartment of Epidemiology and Public Health, University College London, London, U.K. MRC Epidemiology Unit, Cambridge University, Cambridge, U.K.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
Kari LuotolaDepartment of Obstetrics and Gynecology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Carola MarziResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany German Center for Diabetes Research (DZD e.V.), partner site, Munich, Germany.
Christian MüllerClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
Annette PetersInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany German Center for Diabetes Research (DZD e.V.), partner site, Munich, Germany German Center for Cardiovascular Research (DZHK e.V.), partner site Munich, Germany.
Holger ProkischInstitute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Human Genetics, Technical University Munich, Munich, Germany.
Olli RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Wolfgang RathmannInstitute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Michael RodenInstitute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
Marko SalmiNational Institute for Health and Welfare, Turku, Finland MediCity Research Laboratory, University of Turku, Turku, Finland Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Katharina SchrammInstitute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Human Genetics, Technical University Munich, Munich, Germany.
Daniel SwerdlowInstitute of Cardiovascular Sciences, University College London, London, U.K.
Adam G TabakDepartment of Epidemiology and Public Health, University College London, London, U.K. 1st Department of Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary.
Barbara ThorandInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Nick WarehamMRC Epidemiology Unit, Cambridge University, Cambridge, U.K.
Philipp S WildDepartment of Medicine 2, University Medical Center Mainz, Mainz, Germany Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany German Center for Cardiovascular Research (DZHK e.V.), partner site Rhine-Main, Mainz, Germany.
Tanja ZellerClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
Aroon D HingoraniInstitute of Cardiovascular Sciences, University College London, London, U.K.
Daniel R WitteCentre de Recherche Public de la Santé, Strassen, Luxembourg.
Meena KumariDepartment of Epidemiology and Public Health, University College London, London, U.K.
Markus PerolaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland Unit of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland Estonian Genome Center, University of Tartu, Tartu, Estonia.
Veikko SalomaaDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
University College London · GBHelmholtz Zentrum München · DEDeutsches Diabetes-Zentrum e.V. · DEFinnish Institute for Health and Welfare · FIGerman Center for Diabetes Research · DEGerman Centre for Cardiovascular Research · DEUniversity of Helsinki · FIHeinrich Heine University Düsseldorf · DEHelsinki University Hospital · FILaboratoire National de Santé · LUTampere University · FITampere University Hospital · FITechnical University of Munich · DEThe University of Queensland · AUTurku University Hospital · FIUniversität Hamburg · DEUniversität Ulm · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Tartu · EEUniversity of Turku · FI
Funding
Socio-economic status and heterogeneity in agingR01AG013196 · NIA · UNIVERSITY OF LONDON INST OF NEUROLOGY · PI MARMOT, MICHAEL G, SINGH-MANOUX, ARCHANA · 1996 to 2013
$3.5MSocioeconomic gradient in CHD in early old ageR01HL036310 · NHLBI · UNIVERSITY OF LONDON · PI KIVIMAKI, MIKA J, MARMOT, MICHAEL G · 1986 to 2012
$3.1MSOCIAL FACTORS INFLUENCING MEDICAL OUTCOME MEASURESR01HS006516 · AHRQ · UNIVERSITY OF LONDON · PI MARMOT, MICHAEL G · 1990 to 1995
–AHRQ HHS HS06516British Heart Foundation RG/07/008/23674British Heart Foundation RG/10/12/28456British Heart Foundation RG/13/2/30098Medical Research Council G0501184Medical Research Council K013351Medical Research Council MC_U106179471Medical Research Council MC_UU_12015/1Medical Research Council MR/K006584/1Medical Research Council MR/K013351/1NHLBI NIH HHS R01 HL036310NHLBI NIH HHS R01-HL-036310NIA NIH HHS 5R01-AG-13196NIA NIH HHS R01 AG013196
Abstract
The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10(-21)] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10(-17)]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA-raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA-raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance.
Indexed as
AdolescentAdultAgedAged, 80 and overCohort StudiesC-Reactive ProteinDiabetes Mellitus, Type 2FemaleGenome-Wide Association StudyHumansInsulin ResistanceInterleukin-1Interleukin 1 Receptor Antagonist ProteinMaleMiddle AgedPolymorphism, Single NucleotideC-Reactive ProteinIL1F10 protein, humanIL1RN protein, humanInterleukin-1Interleukin 1 Receptor Antagonist Protein
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