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

Although HLA-DRB1 and -DQA1 alleles have been associated with adult and juv enile idiopathic inflammatory myopathies (JIIM), they only partially accoun t for the genetic risk for these autoimmune disorders. Because IL-1 alpha a nd IL-1 beta, and the anti-inflammatory competitive inhibitor, IL-1 recepto r antagonist (IL-1Ra), have been implicated in the pathogenesis of myositis , we assessed the role of variable number tandem repeat (VNTR) polymorphism s of the IL-1Ra gene (IL-1RN) in the aetiology of JIIM: IL-1RN VNTR polymor phisms were performed on 250 JIIM patients and 471 race-matched controls an d were correlated with clinical characteristics. The IL-1RN A1 allele, asso ciated with increased proinflammatory activity, was found to be a risk fact or for Caucasians with JIIM (96.0% carriage rate versus 90.2% in race-match ed controls, P-corr = 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 po ssible risk factor (7.0% versus 1.1% in race-matched controls, P-corr = 0.0 7, OR = 6.5, CI = 1.1-40.3). IL-1RN genotypes did not correlate with circul ating 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 id entified for JIIM, and different alleles may confer susceptibility for diff erent ethnic groups.