Genes associated with rheumatic and diffuse collagen diseases

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Genome analyses of the patients with rheumatic and diffuse collagen diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were performed, and several genes were found to be associated with the diseases. These findings contribute to the elucidation of pathogenesis of these diseases. (1) Association between FCGR2B and SLE was detected. Susceptibility allele product showed a weaker inhibitory effect on B cell activation. (2) Association between CD72 and nephritis-positive SLE was detected. Resistant haplotype produced higher level of alternatively-spliced mRNA. (3) Several TNF and TNF receptor family genes were analyzed, and associations of BLyS and APRIL with SLE were detected. APRIL susceptibility allele produced higher level of mRNA and protein. (4) NK receptor genes including NKG2A, NKG2C and CD94 were not associated with RA nor SLE, but the frequency of NKG2C-deleted haplotype reached 20%. (5) Presence/absence polymorphism of KIR genes was shown to be associated with microscopic polyangitis. (6) Association of LILRB1 with HLA-DRB1 "shared epitope"-positive RA was detected. Susceptibility haplotype expressed lower level of the molecule. (7) A total of 20 genes were found to be up-regulated in RA synovium. in which ID genes were further subjected for in-vitro functional analyses. These genes were found to be essential for the activation of endothelial cells and angiogenesis.