A GENETIC ASSOCIATION BETWEEN JUVENILE RHEUMATOID-ARTHRITIS AND A NOVEL INTERLEUKIN-1-ALPHA POLYMORPHISM

Objective. The genetic factors that predispose to the development of j uvenile rheumatoid arthritis (JRA) and its complications are not compl etely understood. The cytokine interleukin-1 (IL-1) has been implicate d in the pathogenesis of JRA and other inflammatory diseases. This stu dy was performed to test whether polymorphisms of the IL-1 alpha gene might be associated with JRA. Methods. We sequenced the 5' regulatory region (containing the promoter) of the human IL-1 alpha gene in 18 no rmal subjects. This revealed a C (IL-1A1) to T (IL-1A2) transition pol ymorphism at position -889. We studied the frequencies of both alleles in patients with JRA (n = 269) and controls (n = 99). Results. An inc reased gene carriage of IL-1A2 was found in patients with early-onset, pauciarticular JRA (EOPA-JRA; n = 103) compared with controls (0.66 v ersus 0.49; P = 0.01, odds ratio [OR] = 2.1). Within this subset of JR A, 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 wit h elevation of the erythrocyte sedimentation rate (P < 0.0025). Conclu sion. This is the first report of a cytokine gene association with JRA , and we conclude that IL-1 alpha itself, or a gene for which the IL-1 alpha polymorphism is a marker, may contribute to the pathogenesis of EOPA-JRA and the ocular complications found in this group.