*** of HLA-DRB1*13 with susceptibility to uveitis in juvenile idiopathic arthritis in two independent data sets.
Zeggini E, Packham J, Donn R, Wordsworth P, Hall A, Thomson W; BSPAR Study Group.
Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
elez@well.ox.ac.ukAbstract
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease of childhood. Uveitis is the commonest eye complication of JIA, potentially leading to eye surgery and/or visual loss. JIA is a complex genetic trait with well-established HLA-DRB1 ***. The aim of this study was to investigate the involvement of HLA-DRB1 in JIA-associated uveitis.
METHODS: A set of 130 UK Caucasian simplex families consisting of healthy parent(s) and a child affected with juvenile oligoarticular idiopathic arthritis (of which 31 had developed uveitis) had previously been screened for multiple markers in the major histocompatibility complex region. *** with uveitis were investigated through haplotype pattern mining (HPM) and the extended transmission disequilibrium test (ETDT). A further set of 228 UK Caucasian patients with long-standing JIA were fully genotyped for HLA-DRB1 using PCR with sequence-specific primers. *** of HLA-DRB1 alleles in patients with uveitis (n = 50) were examined individually using the chi 2 test.
RESULTS: In the first cohort, HPM identified significant *** of HLA-DRB1*13 with uveitis in juvenile oligoarthritis (P = 0.002). The ETDT confirmed overtransmission of this allele in the families (empirical global P = 0.018). In the second cohort, the significant *** of uveitis with HLA-DRB1*13 was replicated (P = 0.0002, odds ratio 3.4, 95% confidence interval 1.7-6.5).