| Co-Investigator(Kenkyū-buntansha) |
TAGAWA Yoshitsugu Hokkaido Univ., Grad. School of Med., Asso.Prof., 大学院医学研究科, 助教授 (40109426)
YOSHIDA Kazuhiko Hokkaido Univ., Hokkaido Univ. Hospital, Lec., 北海道大学病院, 講師 (90281807)
NAMBA Kenichi Hokkaido Univ., Grad. School of Med., Inst., 大学院医学研究科, 助手 (70333599)
MIZUKI Nobuhisa Yokohama city Univ., Grad. School of Med., Prof., 医学部, 教授 (90336579)
INOKO Hidetoshi Toukai Univ., Grad. School of Med., Prof., 医学部, 教授 (10101932)
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| Research Abstract |
Epidemiologically, refractory intraocular inflammatory diseases such as Behcet's disease, Vogt-Koyanagi-Harada (VKH) disease and sarcoidosis have been believed to be common among the Mongoloid populations. In this study, we investigated these diseases from molecular biological and epidemiological aspects.
As a result, we firstly found that the Behcet's disease was strongly associated with HLA-B locus genes. Furthermore we performed whole genome screening by utilizing 23,000 microsatellite markers, and identified 147 candidate loci (p<0.05). Among Korean patients with Behcet's disease, as well as Japanese patients, the frequency of HLA-B51 was significantly increased compared with healthy controls(p=0.0006). The genetic analysis of the melanocortine 5 receptor which was likely to be associated with Behcet's disease from animal models, did not show significant association in Japanese population.
On the other hand, Vogt-Koyanagi-Harada disease was strongly associated with HLA-DRB1*0405 (p=-
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0.000000079). But we did not find any association with VKH disease at following genes, such as tyrosinase, tyrosinase related protein 1 and tyrosinase related protein 2, respectively. However, we have found that the polymorphism of the interferon-gamma gene was significantly associated with integumentary findings of VKH disease (p=0.003).
Epidemiologically, the distribution of Behcet's disease was around the East Asia, Eurasia, West Asia and the Mediterranean Sea. In contrast, Behcet's disease was rare in Europe, American continents and South-Middle Africa. These results were compatible with our previous findings, and suggested that this disease can be called as "Silk Road Disease". On the other hand, the distribution of VKH disease was mainly in South-East Asia, East Asia, North and Latin America. Regardless of the distribution, HLA-DR4 was strongly associated with VKH disease.
We also investigated the molecular biology and epidemiology of adenoviral conjunctivitis, which is caused by extrinsic factors and without intrinsic factors. We found that the dominant serotype of adenovirus was different from one place to another. For example, the human AdV-type 4 was prevalent in the United Kingdom, human AdV-type 8 was prevalent in South-East Asia, and human AdV-type 37 was prevalent in Japan. These dominant serotypes were changing every 4 or 5 years and genome type mutation of the virus was constantly observed.
These results suggest that refractory intraocular inflammation will be caused both by the intrinsic factors and extrinsic factors. Further studies on these etiological factors will clarify the true etiology, and develop new possible treatment for the prevention of blindness due to difficult intraocular inflammatory diseases. Less
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