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Recent large-scale studies in the Caucasian populations identified many new susceptibility genes to systemic lupus erythematosus (SLE). In this review, we discuss our findings on some of such genes, interferon regulatory factor 5 (IRF5), signal transducer and activator of transcription 4 (STAT4) and B lymphoid tyrosine kinase (BLK), in the Japanese population. All of these genes were associated with SLE also in Japanese; however, there are notable differences. In IRF5, the risk haplotype in Caucasians was not present in Japanese. Instead, a SNP that does not exist in Caucasians defined a protective haplotype in Japanese. In STAT4 and especially in BLK, the risk allele frequency was substantially larger in the Japanese population than in Caucasians; as a result, the genetic contribution of these genes in the population is considered to be greater in the Japanese. Presence of susceptibility genes shared by the Caucasian and Asian populations as well as population-specific susceptibility genes was supported by the first genome-wide association study in the Asians published from China in 2009. We and other investigators also found that IRF5, STAT4 and BLK are associated not only with SLE, but also rheumatoid arthritis and systemic sclerosis. Thus, a substantial proportion of susceptibility genes are shared by multiple autoimmune rheumatic diseases.

Association of IRF5, STAT4 and BLK with systemic lupus erythematosus and other rheumatic diseases.