Studies on molecular genetic mechanism of intractable immune-mediated inflammatory diseases of the eye by genomic analyses

点击翻译按钮获取中文摘要

Intractable immune-mediate inflammatory diseases of the eye including Behcet's disease and Vogt-Koyanagagi-Harada's disease are strongly associated with HLA on the onset. First, we determined whole base sequences of HLA-class I region (1.9x10^6bp) to investigate the exact gene structure of HLA region. As a result utilizing the microsatellites in the region, we found 758 microsatellites which composed of 2-5 repeated bases. Furthermore, we performed the etiological gene mapping of Behcet's disease with 10 microsatellites of HLA class I region in the following ethnics; Japanese, Greece, Iranian, Italian, Saudi Arabian, Turkish and Chinese. Consequently, the etiological gene was successly been be narrowed down to 46kb region between MICA and HLA-B. In addition, we reported that the etiological gene of Behcet's disease exists nearby HLA-B gene. Especially HLA-B51 seems to have a significant correlation with Behcet's disease. We then compared the base sequences of HLA-B51 and its promoter region between the patients and the healthy controls. As a result, there were some single nucleotide polymorphisms (SNPs) in the intron and promoter regions; however there was no specific SNPs found in Behcet's disease. Therefore, the SNPs which characterize HLA-B51 in common may work for the responsible genetic mechanism of Behcet's disease. Moreover, we examined MICA allele frequencies in Turkish patients with Behcet's disease. As a result, MICA^★009 allele was significantly elevated in the patients group compared with the healthy controls. (R. R. = 7.1 p = 0.000046) Therefore, it was suggested that MICA^★009- HLA^★51 mini-haplotype plays a key role in the immunogenetic molecular mechanisms of Behcet's disease.Similar studies are under investigation on other inflammatory ocular diseases.