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 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.
Rider
L G
LG
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Artlett
C M
CM
Foster
C B
CB
Ahmed
A
A
Neeman
T
T
Chanock
S J
SJ
Jimenez
S A
SA
Miller
F W
FW
D000293:Adolescent; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D018598:Minisatellite Repeats; D009220:Myositis / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins