Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis.

W P Maksymowych, M Suarez-Almazor, C T Chou, A S Russell

Department of Medicine, University of Alberta, Edmonton, Canada.

OBJECTIVE--To investigate the potential influence of the HLA-linked LMP2 gene on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS). METHODS--A polymorphic CfoI restriction enzyme site in the coding region of the LMP2 gene was evaluated in genomic DNA samples from 193 white and 49 Chinese B27 individuals with well documented AS, 97 of whom had had acute anterior uveitis (AAU) and 97 peripheral arthritis; 42 samples from normal, white, B27 positive blood donors in whom AS was excluded were also evaluated. RESULTS--Analysis of B27 white AS individuals with AAU, peripheral arthritis, or both, revealed significant differences in genotypic distribution of this bi-allelic locus compared with B27 AS patients without extraspinal manifestations (p < 0.005) or B27 controls (p < 0.01). Furthermore, homozygosity for one LMP2 gene allele was significantly more prevalent in AS patients with AAU (71.3%) (p < 0.01) or peripheral arthritis (68.3%) (p < 0.02) than in B27 controls (45.2%). A similar genotypic distribution was noted in B27 Chinese AS individuals with extraspinal manifestations compared with those with axial disease alone. CONCLUSIONS--These findings support the involvement of the HLA linked LMP2 gene in the expression of disease in B27 individuals and represent a novel finding in rheumatic disease.

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