Molecular genetics and molecular epidemiology of intractable intraocular inflammation frequently found in Mongoloids for prevention of blindness.

从流行病学上讲，白塞病、Vogt-Koyanagi-Harada(VKH)病和结节病等难治性眼内炎症性疾病在蒙古族人群中很常见。在本研究中，我们从分子生物学和流行病学的角度对白塞病进行了研究，首次发现白塞病与人类白细胞抗原B位点基因有很强的相关性。此外，我们利用23,000个微卫星标记进行了全基因组筛选，确定了147个候选基因座(p&lt；0.05)。在韩国白塞病患者和日本患者中，人类白细胞抗原-B51的频率显著高于健康对照组(p=0.0006)。动物模型中可能与白塞病相关的黑素皮质醇5受体的遗传分析在日本人群中没有显示出显著的相关性。另一方面，Vogt-Koyanagi-Harada病与人类白细胞抗原-DRB1*0405(p=-…)有很强的相关性超过0.000000079)。但未发现酪氨酸酶、酪氨酸酶相关蛋白1和酪氨酸酶相关蛋白2等基因与VKH病的相关性。然而，我们发现干扰素-γ基因的多态性与VKH病的外周表现显著相关(p=0.003)。白塞病的流行病学分布在东亚、欧亚、西亚和地中海。相比之下，白塞病在欧洲、美洲大陆和中南部非洲很少见。这些结果与我们以前的发现是一致的，这表明这种疾病可以被称为丝绸之路病。另一方面，VKH病主要分布在东南亚、东亚、北美和拉丁美洲。无论分布如何，人类白细胞抗原DR4与VKH疾病密切相关。我们还调查了由外在因素和非内在因素引起的腺病毒结膜炎的分子生物学和流行病学。我们发现腺病毒的主要血清型在不同的地方是不同的。例如，人类ADV-4型在英国流行，人类ADV-8型在东南亚流行，人-ADV-37型在日本流行。这些主要血清型每隔4年或5年就会发生变化，病毒的基因组变异也会持续出现。这些结果表明，难治性眼内炎症是由内在因素和外在因素共同引起的。对这些病因的进一步研究将阐明真正的病因，并开发新的可能的治疗方法来预防难治性眼内炎性疾病所致的失明。较少

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=- … More 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