Evidence map›Paper›PMID 23111417›Full record

SynthesisEuropean heart journal2013

Interleukin-6 receptor pathways in abdominal aortic aneurysm.

Seamus C Harrison, Andrew J P Smith, Gregory T Jones, Daniel I Swerdlow, Riaz Rampuri, Matthew J Bown, Aneurysm Consortium, Lasse Folkersen, Annette F Baas, Gert Jan de Borst and 18 more

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in European heart journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 10 pooled it
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 10 syntheses or guidelines pooled it, 179 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 11 institutions in 4 countries.

Seamus C HarrisonDepartment of Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, University Street, London WC1E 6JJ, UK.
Andrew J P Smith
Gregory T Jones
Daniel I Swerdlow
Riaz Rampuri
Matthew J Bown
Aneurysm Consortium
Lasse Folkersen
Annette F Baas
Gert Jan de Borst
Jan D Blankensteijn
Jacqueline F Price
Yolanda van der Graaf
Stela McLachlan
Obi Agu
Albert Hofman
Andre G Uitterlinden
Anders Franco-Cereceda
Ynte M Ruigrok
F N van't Hof
Janet T Powell
Andre M van Rij
Juan P Casas
Per Eriksson
Michael V Holmes
Folkert W Asselbergs
Aroon D Hingorani
Steve E Humphries
University College London · GBUniversity Medical Center Utrecht · NLErasmus MC · NLKarolinska Institutet · SEUniversity of Edinburgh · GBUniversity of Leicester · GBUniversity of Otago · NZAmsterdam UMC Location VUmc · NLCharing Cross Hospital · GBLondon School of Hygiene & Tropical Medicine · GBUniversity College Hospital · GB

Funding

British Heart Foundation FS 05/125British Heart Foundation FS/11/16/28696British Heart Foundation FS/13/6/29977British Heart Foundation PG/09/022/26739British Heart Foundation RG2008/08Chief Scientist OfficeMedical Research Council G0802432Wellcome Trust 076113Wellcome Trust 085475
6 · The paper itself

Abstract

methodsWe conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach.

resultsUp to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25-0.66, I(2) = 70%, P = 1.1 × 10-5 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80-0.89, I(2) = 0%, P = 2.7 × 10-11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers.

conclusionsA Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management.

Indexed as

AgedAortic Aneurysm, AbdominalCell LineEpidemiologic MethodsFemaleHumansIntercellular Adhesion Molecule-1Interleukin-6MaleMendelian Randomization AnalysisMiddle AgedProto-Oncogene Proteins c-mycReceptors, Interleukin-6Signal TransductionSTAT3 Transcription FactorIntercellular Adhesion Molecule-1Interleukin-6Proto-Oncogene Proteins c-mycReceptors, Interleukin-6STAT3 Transcription FactorAbdominal aortic aneurysmInterleukin-6Mendelian randomizationPolymorphism

Identifiers

PMID23111417
PMCPMC3869968
OpenAlexW2101261070

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.