ARTHRITIS & RHEUMATISM Vol. 44, No. 10, October 2001, pp 2387–2391 © 2001, American College of Rheumatology Published by Wiley-Liss, Inc. Higher Frequency of Allele 2 of the Interleukin-1 Receptor Antagonist Gene in Patients With Juvenile Idiopathic Arthritis Jir ˇı ´ Vencovsky ´, 1 Kater ˇina Jaros ˇova ´, 1 S ˇ a ´rka Ru ˚z ˇic ˇkova ´, 1 Dana Ne ˇmcova ´, 2 Jaroslava Niederlova ´, 1 Seza Ozen, 3 Mehmet Alikasifoglu, 3 Aysin Bakkaloglu, 3 William E. R. Ollier, 4 and Rizgar A. Mageed 5 Objective. An increased incidence of allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) in several inflammatory diseases has recently been re- ported. The aim of this study was to examine a variable number tandem repeat (VNTR) polymorphism of the IL1RN gene in patients with juvenile idiopathic arthritis (JIA). Methods. Findings in 185 Czech patients with JIA were compared with those in 168 Czech controls, 50 JIA patients and 52 controls of Turkish origin, and 79 controls from central England. VNTR polymorphism analysis of IL1RN was performed by polymerase chain reaction using 2 flanking primers to amplify an 86-bp tandem repeat region in intron 2. Results. The frequency and carriage rate of IL1RN*2 were significantly increased in Czech JIA patients compared with the Czech controls (frequency 27.6% versus 15.8%; carriage rate 44.3% versus 26.2%). Increased frequency and carriage rate of IL1RN*2 were found in 23.3% and 40.0% of Turkish JIA patients and in 17.3% and 34.6% of ethnically matched controls. The high representation of IL1RN*2 in 52.3% of the 22 patients with extended oligoarthritis, 31.3% of the 56 patients with enthesitis-related arthritis, and 42.9% of the 14 patients with other arthritis was particularly responsible for the increased frequency of IL1RN*2 in the Czech JIA patients. We found no association of IL1RN*2 with disease activity or severity parameters. Conclusion. Inheritance of IL1RN*2 may contrib- ute to genetic susceptibility in several forms of auto- immune diseases, including JIA. The IL1RN*2 allele may be useful as a prognostic indicator of the evolution of an extended oligoarticular course of JIA. Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of chronic arthropathies that are classified into 8 categories, based mainly on the clinical disease patterns (1). Epidemiologic studies point to a genetic component in the susceptibility to this disease. HLA status has been an important variable for recent identification of underlying subtypes of JIA, with the frequency of several HLA haplotypes being markedly different between latent classes (2). It has been pro- posed that several genes may contribute to disease in a 2-component process: genes that generally predispose to autoimmunity and disease genes that are specific to the individual JIA subtypes (3). The maintenance of a balance between interleukin-1 (IL-1) and the IL-1 receptor antagonist (IL-1Ra) is important in preventing the development of inflammatory disease (4). Spontaneous development of an inflammatory arthritis with many features resembling rheumatoid arthritis in humans has been described in IL-1Ra knockout mice bred on the BALB/cA back- ground (5). Recently, a beneficial effect of subcutaneous injections of IL-1Ra in patients with rheumatoid arthri- tis was shown (6). Several recent studies have reported an associa- tion of polymorphism in the gene that encodes IL-1Ra with diseases of autoimmune pathogenesis. The gene for the IL-1Ra, named IL1RN, is located on the long arm of chromosome 2 in the region q14–q21, adjacent to the Supported by grant NE/4879-3 from the Internal Grant Agency of the Czech Ministry of Health. 1 Jir ˇı ´ Vencovsky ´, MD, CSc, Kater ˇina Jaros ˇova ´, MD, S ˇ a ´rka Ru ˚z ˇic ˇkova ´, RNDr, Jaroslava Niederlova ´, MA: Institute of Rheuma- tology, Prague, Czech Republic; 2 Dana Ne ˇmcova ´, MD: Charles’ University, Prague, Czech Republic; 3 Seza Ozen, MD, Mehmet Alikasifoglu, MD, Aysin Bakkaloglu, MD: Hacettepe University, Ankara, Turkey; 4 William E. R. Ollier, PhD: University of Manches- ter, Manchester, UK; 5 Rizgar A. Mageed, PhD: The Windeyer Insti- tute of Medical Sciences, London, UK. Address correspondence and reprint requests to Jir ˇı ´ Vencov- sky ´, MD, CSc, Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic. E-mail: venc@revma.cz. Submitted for publication January 5, 2001; accepted in re- vised form May 24, 2001. 2387