POLYMORPHISM IN THE LMP2 GENE INFLUENCES SUSCEPTIBILITY TO EXTRASPINAL DISEASE IN HLA-B27 POSITIVE INDIVIDUALS WITH ANKYLOSING-SPONDYLITIS

Objective-To investigate the potential influence of the HLA-linked LMP 2 gene on disease susceptibility in HLA-B27 individuals with ankylosin g spondylitis (AS). Methods-A polymorphic CfoI restriction enzyme site in the coding region of the LMP2 gene was evaluated in genomic DNA sa mples from 193 white and 49 Chinese B27 individuals with well document ed AS, 97 of whom had had acute anterior uveitis (AAU) and 97 peripher al arthritis; 42 samples from normal, positive blood donors in was exc luded were also evaluated. Results-Analysis of B27 white AS individual s with AAU, peripheral arthritis, or both, revealed significant differ ences in genotypic distribution of this bi-allelic locus compared with B27 AS patients without extraspinal manifestations (p<0.005) or B27 c ontrols (p<0.01). Furthermore, homozygosity for one LMP2 gene allele w as significantly more prevalent in AS patients with AAU (71.3%) (p<0.0 1) or peripheral arthritis (68.3%) (p<0.02) than in B27 controls (45.2 %). A similar genotypic distribution was noted in B27 Chinese AS indiv iduals with extraspinal manifestations compared with those with axial disease alone. Conclusions-These findings support the involvement of t he HLA linked LMP2 gene in the expression of disease in B27 individual s and represent a novel finding in rheumatic disease.