SynthesisLancet (London, England)2012
The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.
Synthesis in Lancet (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 571 papers, 11 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
571 citing papers in PubMed, 11 syntheses or guidelines pooled it, 1,135 citations in OpenAlex.
- Cardiovascular Disease in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Comprehensive Narrative Review.International journal of molecular sciences · 2025Pooled it
- Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus.Nature communications · 2025Pooled it
- Pooled it
- Exploring the Relationship Between Antipsychotic Drug Target Genes and Epilepsy: Evidence From Food and Drug Administration Adverse Event Reporting System Database and Mendelian Randomization.Brain and behavior · 2025Pooled it
- Effects of probiotics on lipid metabolism, oxidation, and inflammation in coronary heart disease: a systematic review and meta-analysis.Frontiers in nutrition · 2025Pooled it
- Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.The Cochrane database of systematic reviews · 2024Pooled it
- Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders.Open biology · 2024Pooled it
- Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.ESC heart failure · 2024Pooled it
- The landscape of the methodology in drug repurposing using human genomic data: a systematic review.Briefings in bioinformatics · 2024Pooled it
- Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function.Communications biology · 2023Pooled it
- Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.PLoS medicine · 2023Pooled it
- The effects of high-intensity interval training on NLRP3 inflammasome and monocyte chemokine receptors in individuals with obesity.PloS one · 2026Trial
- Effect of low-dose colchicine on pericoronary inflammation and coronary plaque composition in chronic coronary disease: a subanalysis of the LoDoCo2 trial.Heart (British Cardiac Society) · 2025Trial
- Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Analysis for Clazakizumab in Patients With End-Stage Kidney Disease Undergoing Dialysis.Clinical and translational science · 2025Trial
- Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.Cardiovascular research · 2022Trial
- Impact of Downregulated Inflammation via the IL6R Asp358Ala Variant on Atrial Fibrillation Recurrence Following Ablation.JACC. Advances · 2026Article
- Evaluating the consequences of childhood adiposity on the human plasma proteome at four timepoints across the lifecourse.Nature communications · 2026Article
- Interleukin-6 as an Oral-Vascular Inflammatory Bridge: Integrating CXCL10 and Haptoglobin 2-2 into a Potential Model of Periodontitis-Associated Cardiovascular Risk.International journal of molecular sciences · 2026Review
- Host Genetic Regulation of NLRP3 Inflammasome Cytokines Reveals Immune and Vascular Pathways in HIV.medRxiv : the preprint server for health sciences · 2026Article
- Review
511 more citing papers are in PubMed but not listed here.
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Authors and funding
117 authors at 20 institutions in 10 countries.
Funding
Abstract
backgroundA high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown.
methodsApplying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis.
findingsIn 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5)).
interpretationOn the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.
fundingUK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.