A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis.

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Abstract Text:

Fina A S Kurreeman,Leonid Padyukov,Rute B Marques,Steven J Schrodi,Maria Seddighzadeh,Gerrie Stoeken-Rijsbergen,Annette H M van der Helm-van Mil,Cornelia F Allaart,Willem Verduyn,Jeanine Houwing-Duistermaat,Lars Alfredsson,Ann B Begovich,Lars Klareskog,Tom W J Huizinga,Rene E M Toes,Fina A S Kurreeman,Leonid Padyukov,Rute B Marques,Steven J Schrodi,Maria Seddighzadeh,Gerrie Stoeken-Rijsbergen,Annette H M van der Helm-van Mil,Cornelia F Allaart,Willem Verduyn,Jeanine Houwing-Duistermaat,Lars Alfredsson,Ann B Begovich,Lars Klareskog,Tom W J Huizinga,Rene E M Toes,Fina A S Kurreeman,Leonid Padyukov,Rute B Marques,Steven J Schrodi,Maria Seddighzadeh,Gerrie Stoeken-Rijsbergen,Annette H M van der Helm-van Mil,Cornelia F Allaart,Willem Verduyn,Jeanine Houwing-Duistermaat,Lars Alfredsson,Ann B Begovich,Lars Klareskog,Tom W J Huizinga,Rene E M Toes,

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting approximately 1% of the population. The disease results from the interplay between an individual's genetic background and unknown environmental triggers. Although human leukocyte antigens (HLAs) account for approximately 30% of the heritable risk, the identities of non-HLA genes explaining the remainder of the genetic component are largely unknown. Based on functional data in mice, we hypothesized that the immune-related genes complement component 5 (C5) and/or TNF receptor-associated factor 1 (TRAF1), located on Chromosome 9q33-34, would represent relevant candidate genes for RA. We therefore aimed to investigate whether this locus would play a role in RA. METHODS AND FINDINGS: We performed a multitiered case-control study using 40 single-nucleotide polymorphisms (SNPs) from the TRAF1 and C5 (TRAF1/C5) region in a set of 290 RA patients and 254 unaffected participants (controls) of Dutch origin. Stepwise replication of significant SNPs was performed in three independent sample sets from the Netherlands (ncases/controls = 454/270), Sweden (ncases/controls = 1,500/1,000) and US (ncases/controls = 475/475). We observed a significant association (p < 0.05) of SNPs located in a haplotype block that encompasses a 65 kb region including the 3' end of C5 as well as TRAF1. A sliding window analysis revealed an association peak at an intergenic region located approximately 10 kb from both C5 and TRAF1. This peak, defined by SNP14/rs10818488, was confirmed in a total of 2,719 RA patients and 1,999 controls (odds ratiocommon = 1.28, 95% confidence interval 1.17-1.39, pcombined = 1.40 x 10(-8)) with a population-attributable risk of 6.1%. The A (minor susceptibility) allele of this SNP also significantly correlates with increased disease progression as determined by radiographic damage over time in RA patients (p = 0.008). CONCLUSIONS: Using a candidate-gene approach we have identified a novel genetic risk factor for RA. Our findings indicate that a polymorphism in the TRAF1/C5 region increases the susceptibility to and severity of RA, possibly by influencing the structure, function, and/or expression levels of TRAF1 and/or C5.

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Publishing Authors By Initials

FA Kurreeman,L Padyukov,RB Marques,SJ Schrodi,M Seddighzadeh,G Stoeken-Rijsbergen,AH van der Helm-van Mil,CF Allaart,W Verduyn,J Houwing-Duistermaat,L Alfredsson,AB Begovich,L Klareskog,TW Huizinga,RE Toes,FA Kurreeman,L Padyukov,RB Marques,SJ Schrodi,M Seddighzadeh,G Stoeken-Rijsbergen,AH van der Helm-van Mil,CF Allaart,W Verduyn,J Houwing-Duistermaat,L Alfredsson,AB Begovich,L Klareskog,TW Huizinga,RE Toes,FA Kurreeman,L Padyukov,RB Marques,SJ Schrodi,M Seddighzadeh,G Stoeken-Rijsbergen,AH van der Helm-van Mil,CF Allaart,W Verduyn,J Houwing-Duistermaat,L Alfredsson,AB Begovich,L Klareskog,TW Huizinga,RE Toes,

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

PUBMED ID PMID:

MEDLINE DATE:

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: PLoS medicine

VOLUME: 4

Page Numbers: e278

Journal Abbreviation: PLoS Med.

ISSN: 1549-1676

DAY: 18

MONTH: Sep

YEAR: 2007

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101231360

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. Information

Substance Name: TNF Receptor-Associated Factor 1

Registry Number: 0

Grant and Affiliation Information for A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis.

AFFILIATION: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: PLoS Med

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis Related Publications

• A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis.
• Association of smoking with the constitution of the anti-cyclic citrullinated peptide response in the absence of HLA-DRB1 shared epitope alleles.
• Cutting Edge: TNFR-Shedding by CD4+CD25+ Regulatory T Cells Inhibits the Induction of Inflammatory Mediators.
• Fine specificity of the anti-citrullinated protein antibody response is influenced by the shared epitope alleles.
• Mechanisms of oral tolerance revisited.
• Replication of the tumor necrosis factor receptor-associated factor 1/complement component 5 region as a susceptibility locus for rheumatoid arthritis in a European family-based study.
• Reply.
• Suppressor activity among CD4+,CD25++ T cells is discriminated by membrane-bound tumor necrosis factor alpha.