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Interferon-Gamma and Interleukin-4 Gene polymorphisms in UK caucasian idiopathic inflammatory myopathy patients
  1. Hector Chinoy (hector.chinoy{at}manchester.ac.uk)
  1. The University of Manchester, United Kingdom
    1. Fiona Salway (fiona.salway{at}manchester.ac.uk)
    1. The University of Manchester, United Kingdom
      1. Sally John (sally.john{at}manchester.ac.uk)
      1. The University of Manchester, United Kingdom
        1. Noreen Fertig (fertig{at}dom.pitt.edu)
        1. University of Pittsburgh, United States
          1. Brian D Tait (bdtait{at}arcbs.redcross.org.au)
          1. Australian Red Cross Blood Service, Australia
            1. Chester V. Oddis (oddis{at}dom.pitt.edu)
            1. University of Pittsburgh, United States
              1. William E R Ollier (william.ollier{at}manchester.ac.uk)
              1. The University of Manchester, United Kingdom
                1. Robert G Cooper (robert.g.cooper{at}manchester.ac.uk)
                1. The University of Manchester, United Kingdom

                  Abstract

                  Objectives: To determine whether interferon-gamma (IFN-γ) and interleukin-4 (IL-4) genes confer susceptibility for the idiopathic inflammatory myopathies (IIMs).

                  Methods: A large cross-sectional study of UK Caucasian adults with polymyositis (PM, n=101), dermatomyositis (DM, n=94) and myositis overlapping with a connective tissue disease (myositis/CTD-overlap, n=70) was completed. 177 ethnically matched controls were available for comparison. Single nucleotide polymorphisms (SNPs) within intronic regions coding for IL-4, IFN-γ and a microsatellite marker within intron 1 of the IFN-γ gene were typed.

                  Results: Strong linkage disequilibrium was present between SNPs in each gene. In the IFN-γ gene, a weak allelic association was observed in PM vs. controls at rs1861493 (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.03-2.4). The microsatellite IFN-γ CA(14) allele was associated with risk for IIMs overall (OR 3.3, 95% CI 1.4-7.8), the strongest association being observed within the anti-U1-RNP group (OR 6.0, 95% CI 1.5-23.1), and persisting after adjustment for known myositis HLA class II associations.

                  Conclusions: Genetic markers in the IFN-γ gene demonstrate significant allelic associations with the IIMs in a UK Caucasian population. The SNPs tested in this study within the region coding for IL-4 fail to show significant associations to IIM disease susceptibility.

                  • genetics
                  • interferon-gamma
                  • interleukin-4
                  • myositis
                  • single nucleotide polymorphisms

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