Evidence map›Paper›PMID 26916345›Full record

ArticleAnnals of the rheumatic diseases2016

An ankylosing spondylitis-associated genetic variant in the IL23R-IL12RB2 intergenic region modulates enhancer activity and is associated with increased Th1-cell differentiation.

Amity R Roberts, Matteo Vecellio, Liye Chen, Anna Ridley, Adrian Cortes, Julian C Knight, Paul Bowness, Carla J Cohen, B Paul Wordsworth

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Recent Updates in Juvenile Spondyloarthritis.Rheumatic diseases clinics of North America · 2021
    Review
  15. Review
  16. Review
  17. Review
  18. Genetics and the axial spondyloarthritis spectrum.Rheumatology (Oxford, England) · 2020
    Review
  19. Review
  20. Review
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

9 authors at 3 institutions in 1 country.

Amity R RobertsNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Matteo VecellioNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Liye ChenNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Anna RidleyNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Adrian CortesDivision of Clinical Neurology, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Julian C KnightWellcome Trust Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Paul BownessNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Carla J CohenNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
B Paul WordsworthNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Nuffield Orthopaedic Centre · GBUniversity of Oxford · GBJohn Radcliffe Hospital · GB

Funding

Arthritis Research UK 20235Arthritis Research UK 20402Arthritis Research UK 20773European Research Council 281824Versus Arthritis 19356Versus Arthritis 20796
6 · The paper itself

Abstract

objectivesTo explore the functional basis for the association between ankylosing spondylitis (AS) and single-nucleotide polymorphisms (SNPs) in the IL23R-IL12RB2 intergenic region.

methodsWe performed conditional analysis on genetic association data and used epigenetic data on chromatin remodelling and transcription factor (TF) binding to identify the primary AS-associated IL23R-IL12RB2 intergenic SNP. Functional effects were tested in luciferase reporter assays in HEK293T cells and allele-specific TF binding was investigated by electrophoretic mobility gel shift assays. IL23R and IL12RB2 mRNA levels in CD4+ T cells were compared between cases homozygous for the AS-risk 'A' allele and the protective 'G' allele. The proportions of interleukin (IL)-17A+ and interferon (IFN)-γ+ CD4+ T-cells were measured by fluorescence-activated cell sorting and compared between these AS-risk and protective genotypes.

resultsConditional analysis identified rs11209032 as the probable causal SNP within a 1.14 kb putative enhancer between IL23R and IL12RB2. Reduced luciferase activity was seen for the risk allele (p<0.001) and reduced H3K4me1 methylation observed in CD4+ T-cells from 'A/A' homozygotes (p=0.02). The binding of nuclear extract to the risk allele was decreased ∼3.5-fold compared with the protective allele (p<0.001). The proportion of IFN-γ+ CD4+ T-cells was increased in 'A/A' homozygotes (p=0.004), but neither IL23R nor IL12RB2 mRNA was affected.

conclusionsThe rs11209032 SNP downstream of IL23R forms part of an enhancer, allelic variation of which may influence Th1-cell numbers. Homozygosity for the risk 'A' allele is associated with more IFN-γ-secreting (Th1) cells. Further work is necessary to explain the mechanisms for these important observations.

Indexed as

AdultAllelesCell DifferentiationDNA, IntergenicFemaleFlow CytometryGenetic Association StudiesGenetic VariationGenotypeHEK293 CellsHumansMalePolymorphism, Single NucleotideReceptors, InterleukinReceptors, Interleukin-12Spondylitis, AnkylosingDNA, IntergenicIL12RB2 protein, humanIL23R protein, humanReceptors, InterleukinReceptors, Interleukin-12Ankylosing SpondylitisGene PolymorphismT Cells

Identifiers

PMID26916345
PMCPMC5136719
OpenAlexW2287803372

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.