A genetic association between juvenile rheumatoid arthritis and a novel interleukin‐1α polymorphism

Abstract

Objective. The genetic factors that predispose to the development of juvenile rheumatoid arthritis (JRA) and its complications are not completely understood. The cytokine interleukin‐1 (IL‐1) has been implicated in the pathogenesis of JRA and other inflammatory diseases. This study was performed to test whether polymorphisms of the IL‐1α gene might be associated with JRA.Methods. We sequenced the 5' regulatory region (containing the promoter) of the human IL‐1α gene in 18 normal subjects. This revealed a C (IL‐1A1) to T (IL‐1A2) transition polymorphism at position ‐889. We studied the frequencies of both alleles in patients with JRA (n = 269) and controls (n = 99).Results. An increased gene carriage of IL‐1A2 was found in patients with early‐onset, pauciarticular JRA (EOPA‐JRA; n = 103) compared with controls (0.66 versus 0.49; P = 0.01, odds ratio [OR] = 2.1). Within this subset of JRA, the association with IL‐1A2 was particularly strong in the patients in whom chronic iridocyclitis developed (n = 28) compared with those without chronic iridocyclitis (0.89 versus 0.57; P = 0.002, OR = 6.2). Within the group of EOPA‐JRA patients, IL‐1A2 was also associated with elevation of the erythrocyte sedimentation rate (P < 0.0025).Conclusion. This is the first report of a cytokine gene association with JRA, and we conclude that IL‐1α itself, or a gene for which the IL‐1α polymorphism is a marker, may contribute to the pathogenesis of EOPA‐JRA and the ocular complications found in this group.