Evidence map›Paper›PMID 23956247›Full record

ArticleAnnals of the rheumatic diseases2014

Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis.

Rachel Knevel, Kerstin Klein, Klaartje Somers, Caroline Ospelt, Jeanine J Houwing-Duistermaat, Jessica A B van Nies, Diederik P C de Rooy, Laura de Bock, Fina A S Kurreeman, Joris Schonkeren and 13 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

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  18. Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.Annual review of genomics and human genetics · 2016
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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

23 authors at 5 institutions in 4 countries.

Rachel KnevelDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Kerstin KleinCenter of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology (ZIHP), Zurich, Switzerland.
Klaartje SomersHasselt University, Biomedical Research Institute, Diepenbeek, Belgium.
Caroline OspeltCenter of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology (ZIHP), Zurich, Switzerland.
Jeanine J Houwing-DuistermaatDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Jessica A B van NiesDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Diederik P C de RooyDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Laura de BockHasselt University, Biomedical Research Institute, Diepenbeek, Belgium.
Fina A S KurreemanDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Joris SchonkerenDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Gerrie Stoeken-RijsbergenDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Quinta HelmerDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Michael P M van der LindenDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Marlena KernFeinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
Nataly Manjarrez-OrdunoFeinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
Luis Rodriguez-RodriquezFeinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
Piet StinissenHasselt University, Biomedical Research Institute, Diepenbeek, Belgium.
Tom W J HuizingaDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Rene E M ToesDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Steffen GayCenter of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology (ZIHP), Zurich, Switzerland.
Peter K GregersenFeinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
Veerle SomersHasselt University, Biomedical Research Institute, Diepenbeek, Belgium.
Annette H M van der Helm-van MilDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLHasselt University · BESwiss Integrative Center for Human Health · CHFeinstein Institute for Medical Research · USNorthwell Health · US

Funding

NARAC The Genetics of Rheumatoid ArthritisR01AR044422 · NIAMS · NORTH SHORE UNIVERSITY HOSPITAL · PI GREGERSEN, PETER K. · 1997 to 2011
$6.0M
Mapping Autoimmune Phenotypes in Multiplex FamiliesR01AI068759 · NIAID · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI GREGERSEN, PETER K. · 2007 to 2011
$4.7M
Genes and Phenotype (GAP) studies of immunologic and inflammatory pathwaysRC2AR059092 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI DIAMOND, BETTY, GREGERSEN, PETER K. · 2009 to 2010
$2.5M
AUTOIMMUNE BIOMARKERS COLLABORATIVE NETWORK-264012256N01AR012256 · NIAMS · NORTH SHORE UNIVERSITY HOSPITA · 2002 to 2003
–
NIAID NIH HHS R01 AI068759NIAMS NIH HHS R01 AR044422NIAMS NIH HHS RC2 AR059092
6 · The paper itself

Abstract

backgroundJoint destruction is a hallmark of autoantibody-positive rheumatoid arthritis (RA), though the severity is highly variable between patients. The processes underlying these interindividual differences are incompletely understood.

methodsWe performed a genome-wide association study on the radiological progression rate in 384 autoantibody-positive patients with RA. In stage-II 1557 X-rays of 301 Dutch autoantibody-positive patients with RA were studied and in stage-III 861 X-rays of 742 North American autoantibody-positive patients with RA. Sperm-Associated Antigen 16 (SPAG16) expression in RA synovium and fibroblast-like synoviocytes (FLS) was examined using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry. FLS secrete metalloproteinases that degrade cartilage and bone. SPAG16 genotypes were related to matrix metalloproteinase (MMP)-3 and MMP-1 expression by FLS in vitro and MMP-3 production ex vivo.

resultsA cluster of single nucleotide polymorphisms (SNPs) at 2q34, located at SPAG16, associated with the radiological progression rate; rs7607479 reached genome-wide significance. A protective role of rs7607479 was replicated in European and North American patients with RA. Per minor allele, patients had a 0.78-fold (95% CI 0.67 to 0.91) progression rate over 7 years. mRNA and protein expression of SPAG16 in RA synovium and FLS was verified. FLS carrying the minor allele secreted less MMP-3 (p=1.60×10(-2)). Furthermore, patients with RA carrying the minor allele had lower serum levels of MMP-3 (p=4.28×10(-2)). In a multivariate analysis on rs7607479 and MMP-3, only MMP-3 associated with progression (p=2.77×10(-4)), suggesting that the association between SPAG16-rs7607479 and joint damage is mediated via an effect on MMP-3 secretion.

conclusionsGenetic and functional analyses indicate that SPAG16 influences MMP-3 regulation and protects against joint destruction in autoantibody-positive RA. These findings could enhance risk stratification in autoantibody-positive RA.

Indexed as

AdultAgedArthritis, RheumatoidAutoantibodiesDisease ProgressionFemaleGenome-Wide Association StudyGenotypeHumansMaleMatrix Metalloproteinase 3Microtubule-Associated ProteinsMiddle AgedPolymorphism, Single NucleotideSynovial MembraneAutoantibodiesMatrix Metalloproteinase 3Microtubule-Associated ProteinsSPAG16 protein, humanGene PolymorphismOutcomes ResearchRheumatoid Arthritis

Identifiers

PMID23956247
PMCPMC11292588
OpenAlexW2125976579

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Registered trials

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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.