Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;13(3):e002872.
doi: 10.1161/CIRCGEN.119.002872. Epub 2020 May 12.

Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes: A Mendelian Randomization Study

Marios K Georgakis  1   2 , Rainer Malik  1 , Dipender Gill  3 , Nora Franceschini  4 , Cathie L M Sudlow  3   5 , Martin Dichgans  1   6   7 ; INVENT Consortium,CHARGE Inflammation Working Group
Collaborators, Affiliations

Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes: A Mendelian Randomization Study

Marios K Georgakis et al. Circ Genom Precis Med. 2020 Jun.
No abstract available

Keywords: cardiovascular diseases; coronary artery disease; genetics; inflammation; stroke.

PubMed Disclaimer

Figures

Figure.
Figure.
Genetic proxies for downregulated IL-6 (interleukin-6) signaling and their effects on ischemic stroke and other cardiovascular outcomes in Mendelian randomization analyses (MR). A, Effects of pharmacological inhibition of IL-6R (tocilizumab 8 mg/kg versus placebo for 8–24 weeks) and of genetic downregulation of IL-6 signaling on IL-6 (Ntrials=1446 and Ngenetics=8293), sIL-6R (soluble IL-6 receptor; Ntrials=1465 and Ngenetics=3301), and fibrinogen (Fg) levels (Ntrials=1108 and Ngenetics=120 246). B, Genetically downregulated IL-6 signaling in association with ischemic stroke and coronary artery disease as derived from inverse-variance weighted (IVW) analyses using the full set of 7 single-nucleotide polymorphisms (SNPs) as instruments or the 3 SNPs located within the IL6R gene. C, SNP-specific effects of the associations with ischemic stroke. D, Genetically downregulated IL-6 signaling and ischemic stroke subtypes. E, Distributions of the effects of 7 randomly selected CRP (C-reactive protein)-decreasing SNPs on risk of ischemic stroke and the position of the effect of the IL-6 signaling downregulating SNPs included in our analyses. F, Genetically downregulated IL-6 signaling with other cardiovascular outcomes. Effect sizes for genetically downregulated IL-6 signaling are scaled to the CRP-decreasing effects of tocilizumab (8 mg/kg). Statistical significance thresholds are set at P<0.05/3=0.017 for the 3 ischemic stroke subtypes, and at P<0.05/9=0.0055 for the 9 cardiovascular outcomes. Associations showing P values <0.05 are considered suggestive. SMD indicates standardized mean difference.
See this image and copyright information in PMC

References

    1. Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1beta inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2019;pii:ehz542. doi: 10.1093/eurheartj/ehz542. - PubMed
    1. Swerdlow DI, Holmes MV, Kuchenbaecker KB, Engmann JE, Shah T, Sofat R, Guo Y, Chung C, Peasey A, Pfister R, et al. Interleukin-6 Receptor Mendelian Randomisation Analysis Consortium. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379:1214–1224. doi: 10.1016/S0140-6736(12)60110-X. - PMC - PubMed
    1. Yang J, Ferreira T, Morris AP, Medland SE, Madden PA, Heath AC, Martin NG, Montgomery GW, Weedon MN, Loos RJ, et al. Genetic Investigation of ANthropometric Traits (GIANT) Consortium; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet. 2012;44:369–75, S1. doi: 10.1038/ng.2213. - PMC - PubMed
    1. Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, et al. Use of genetic variants related to antihypertensive drugs to inform on efficacy and side effects. Circulation. 2019;140:270–279. doi: 10.1161/CIRCULATIONAHA.118.038814. - PMC - PubMed
    1. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, et al. CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131. doi: 10.1056/NEJMoa1707914. - PubMed

Publication types