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.
- single nucleotide polymorphisms