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Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies.
Clinical and Experimental Immunology 2000 July
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-1alpha and IL-1beta, 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.
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