Genetic Determinants of Circulating Interleukin-1 Receptor Antagonist Levels and Their Association With Glycemic Traits
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL1RN variants affect the pathophysiology of human infections and the risk of insulin resistance and knee osteoarthritis.
“These findings have been confirmed in three independent cohorts26, and further research has demonstrated that these factors affect the pathophysiology of human infections27 and the risk of developing insulin resistance28 and knee osteoarthritis29.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 44 · Cited by 46
- Authors
- Herder, C., Nuotio, M.-L., Shah, S., Blankenberg, S., Brunner, E. J., Carstensen, M., Gieger, C., Grallert, H., Jula, A., Kähönen, M., Kettunen, J., Kivimäki, M., Koenig, W., Kristiansson, K., Langenberg, C., Lehtimäki, T., Luotola, K., Marzi, C., Müller, C., Peters, A., Prokisch, H., Raitakari, O., Rathmann, W., Roden, M., Salmi, M., Schramm, K., Swerdlow, D., Tabak, A. G., Thorand, B., Wareham, N., Wild, P. S., Zeller, T., Hingorani, A. D., Witte, D. R., Kumari, M., Perola, M., & Salomaa, V.
- Affiliations
- Deutsches Diabetes-Zentrum e.V. (DE)
- University of Helsinki (FI)
- The University of Queensland (AU)
- Universität Hamburg (DE)
- University College London (GB)
- Helmholtz Munich (DE)
- Finnish Institute for Health and Welfare (FI)
- Tampere University Hospital (FI)
- Department of Epidemiology and Public Health, University College London, London, U.K.
- Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Ulm, Germany
- University of Cambridge (GB)
- Tampere University (FI)
- University of Turku (FI)
- Düsseldorf University Hospital (DE)
- MRC Epidemiology Unit, Cambridge University, Cambridge, U.K.
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Centre de Recherche Public de la Santé (LU)
- Corresponding author
- Herder, Christian
- ORCID
- Herder, Christian
- Nuotio, Marja-Liisa
- Shah, Sonia
- Blankenberg, Stefan
- Brunner, Eric J.
- Gieger, Christian
- Grallert, Harald
- Kähönen, Mika
- Kettunen, Johannes
- Kristiansson, Kati
- Langenberg, Claudia
- Lehtimäki, Terho
- Luotola, Kari
- Müller, Christian
- Peters, Annette
- Prokisch, Holger
- Raitakari, Olli
- Rathmann, Wolfgang
- Roden, Michael
- Salmi, Marko
- Schramm, Katharina
- Swerdlow, Daniel
- Thorand, Barbara
- Wild, Philipp S.
- Zeller, Tanja
- Hingorani, Aroon D.
- Witte, Daniel R.
- Perola, Markus
- Salomaa, Veikko
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-11-13
- Volume
- 63
- Issue
- 12
- Pages
- 4343-4359
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4237993
- OpenAlex
- W2172054086
- Cited by
- 46
- References
- 44
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 9
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Site cant be reached (submittedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Open Access at Essex (University of Essex) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10135)
- British Heart Foundation (RG/10/12/28456, RG/13/2/30098, RG/07/008/23674)
- Agency for Healthcare Research and Quality (HS06516)
- Medical Research Council (MR/K013351/1, MR/K006584/1, MC_UU_12015/1)
- Economic and Social Research Council (ES/K005146/1, ES/J023299/1, ES/H029745/1)
- National Institute on Aging (5R01 AG13196, R01AG013196)
- National Heart, Lung, and Blood Institute (R01HL036310)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- interleukin-1 receptor antagonist, IL-1β, single nucleotide polymorphisms, insulin resistance, HOMA-IR, fasting insulin, C-reactive protein, type 2 diabetes, beta-cell function, glycemic traits, cardiometabolic risk, genetic association
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, C-Reactive Protein, Diabetes Mellitus, Type 2, Female, Humans, Insulin Resistance, Interleukin-1, Male, Middle Aged, Cohort Studies, Polymorphism, Single Nucleotide, Interleukin 1 Receptor Antagonist Protein, Genome-Wide Association Study, Young Adult, Protective Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
