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  • Title: A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism.
    Author: McDowell TL, Symons JA, Ploski R, Førre O, Duff GW.
    Journal: Arthritis Rheum; 1995 Feb; 38(2):221-8. PubMed ID: 7848312.
    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-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 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-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.
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