Abstract
Recent large-scale association studies revealed new susceptibility genes to systemic lupus erythematosus (SLE) including IRF5, STAT4 and BLK. Association of these genes have been quickly replicated by many studies in multiple populations. In this minireview, we discuss our recent studies on the association of these genes with SLE in Japanese. Although association of these genes was replicated, notable differences were observed between Caucasian and Japanese populations.
In Japanese, IRF5 risk haplotype in the Caucasians carrying three functional polymorphisms (a single nucleotide polymorphism [SNP] at exon 1B splice site, 10 amino acid insertion/deletion, a SNP at poly A signal) is almost absent. However, another intron 1 SNP, which was not described in the Caucasians, was significantly associated with SLE in Japanese.
On the other hand, both the STAT4 intronic SNPs and C8orf13-BLK intergenic SNPs associated in Caucasians were similarly associated with SLE in Japanese. Moreover, because of higher population frequencies of the risk genotypes and higher odds ratios, the contribution of these genes appeared to be greater in the Japanese than in the Caucasians.
Although association of these genes with SLE is established, the molecular mechanisms of the association remain largely unknown. In addition, further studies are required to develop applications of the genetics information for clinical use. Genetics finally began to reveal new and reliable clues to gain insight into the pathogenesis of highly complicated disorders such as SLE.
