Abstract
OBJECTIVE: To determine whether interferon-gamma (IFN-gamma) 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-gamma and a microsatellite marker within intron 1 of the IFN-gamma gene were typed. RESULTS: Strong linkage disequilibrium was present between SNPs in each gene. In the IFN-gamma gene, a weak allelic association was observed in PM versus controls at rs1861493 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.03 to 2.4). The microsatellite IFN-gamma CA(14) allele was associated with risk for IIMs overall (OR 3.3, 95% CI 1.4 to 7.8), the strongest association being observed within the anti-U1-ribonucleoprotein (RNP) group (OR 6.0, 95% CI 1.5 to 23.1), and persisting after adjustment for known myositis human leucocyte antigen (HLA) class II associations. CONCLUSIONS: Genetic markers in the IFN-gamma 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 with susceptibility to IIM disease.