Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies

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Abstract
Although HLA-DRB1 and -DQA1 alleles have been associated with adult and juvenile idiopathic inflammatory myopathies (JIIM), they only partially account for the genetic risk for these autoimmune disorders. Because IL-1α and IL-1β, and the anti-inflammatory competitive inhibitor, IL-1 receptor antagonist (IL-1Ra), have been implicated in the pathogenesis of myositis, we assessed the role of variable number tandem repeat (VNTR) polymorphisms of the IL-1Ra gene (IL-1RN) in the aetiology of JIIM: IL-1RN VNTR polymorphisms were performed on 250 JIIM patients and 471 race-matched controls and were correlated with clinical characteristics. The IL-1RN A1 allele, associated with increased proinflammatory activity, was found to be a risk factor for Caucasians with JIIM (96·0% carriage rate versus 90·2% in race-matched controls, Pcorr= 0·037, odds ratio (OR) = 2·5, confidence interval (CI) = 1·1–5·8), but not for African-Americans, in whom the A3 allele was a possible risk factor (7·0% versus 1·1% in race-matched controls, Pcorr= 0·07, OR = 6·5, CI = 1·1–40·3). IL-1RN genotypes did not correlate with circulating levels of IL-1Ra, which were higher in patients than in controls. The polymorphic IL-1RN locus could be the first non-MHC genetic risk factor identified for JIIM, and different alleles may confer susceptibility for different ethnic groups.