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Investigation of association between the TRAF family genes and RA susceptibility
  1. Catherine Potter1,
  2. Stephen Eyre1,
  3. Andrew Cope2,
  4. Jane Worthington1,
  5. Anne Barton1
  1. 1
    Arthritis Research Campaign Epidemiology Unit, University of Manchester, UK
  2. 2
    The Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, UK
  1. Dr Anne Barton, Arthritis Research Campaign Epidemiology Unit, Stopford Building, University of Manchester, Manchester M13 9PT, UK; Anne.Barton{at}manchester.ac.uk

Abstract

Objective: The tumour necrosis factor (TNF) receptor-associated factor (TRAF) family is important in activating multiple inflammatory and immune related processes induced by cytokines such as TNFα and interleukin-1. These genes therefore represent strong candidate susceptibility factors for rheumatoid arthritis (RA). A study was undertaken to investigate the association between single nucleotide polymorphisms (SNPs) spanning six TRAF genes and RA in a British population.

Methods: Twenty-three haplotype tagging (ht) SNPs and 26 random SNPs spanning the six TRAF genes were initially tested for association in a cohort of 351 unrelated patients with RA and 368 controls. Any SNPs demonstrating an association were genotyped in further samples. Sequenom MassARRAY technology was preferentially used for genotyping. Both single point and haplotypic analyses were performed.

Results: Forty-four SNPs were successfully genotyped and conformed to Hardy-Weinberg expectation. A single SNP, rs7514863, mapping upstream of the TRAF5 gene and affecting a putative transcription factor binding site, demonstrated a significant association across the entire cohort of 1273 cases with RA compared with 2463 healthy controls (OR for minor T allele 1.2 (95% CI 1.06 to 1.36), p = 0.005). The association was stronger in the subgroup carrying at least one copy of the shared epitope alleles (OR 1.43 (95% CI 1.18 to 1.73), p = 0.0003).

Conclusion: These findings provide evidence for the association of an SNP upstream of a strong candidate RA susceptibility gene, TRAF5, in a large cohort of patients and controls. Further association and functional studies are required to investigate the role of this variant, or one in linkage disequilibrium with it, in RA disease causation.

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Footnotes

  • Funding for genotyping in this study was provided by the Arthritis Research Campaign, UK. AB is in receipt of a Wellcome Advanced Fellowship.

  • Competing interests: None.

  • Abbreviations:
    IL
    interleukin
    MAF
    minor allele frequency
    RA
    rheumatoid arthritis
    RF
    rheumatoid factor
    SE
    shared epitope
    SNP
    single nucleotide polymorphism
    TNFα
    tumour necrosis factor α
    TRAF
    TNF receptor-associated factor

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