ANTHROPOLOGICAL AND MOLECULAR GENETIC STUDIES ON THE EPIDEMIOLOGY OF INTRACTABLE OCULAR DISEASES

难治性眼病流行病学的人类学和分子遗传学研究

• 批准号: 12576022
• 负责人: OHNO Shigeaki
• 金额: $ 9.79万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12576022/
• 关键词: Behcet's disease; HLA-B51; Greek; B^*5101; Japanese; PCR-SBT method; Italian; Saudi Arabian; 炎症性眼疾患; 原田病; 主要組織適合抗原; 人種差; 遺伝子タイピング; Vogt-小柳-原田病; ぶどう膜炎; HLA-DR4; 分子遺伝学; 人類学; DNA タイピング; 疫学; 人種; シルクロード病

Behcet's disease (BD) is known to be strongly associated with human leukocyte antigen (HLA) B51in many different ethnic groups. HLA-B51 allele typing of Greek BD patients was performed to study the distribution of B^*5101-B^*5107 alleles in this Greek population. The B51 antigen strongly associated with BD was found to be predominantly encoded by allele B^*5101. As it is now known that the B51 antigen can be encoded by 21 alleles, B^*5101-B^*5121, we performed HLA- B^*5101 allele genotyping among 58 Greek patients with BD. After serological HLA typing, typing of HLA-B^*5101 alleles was performed using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The frequency of the B51 antigen was found to be significantly higher in the patient group as compared with the control group. In the genotyping of B51 alleles, 34 out of 44 B51-positive patients possessed B^*5101, and 13 out of the 44 carried B^*5108. In contrast, all of the 9 B51-positive normal controls carried B^* … More 5101. This study revealed a strong association of Greeks with BD, with both B^*5101 and B^*5108.HLA-B^*5101 and HLA-B^*5108 were found to be increased in the patient groups among Italian and Saudi Arabian populations. We performed HLA-B^*51 allele genotyping by PCR-SBT method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. 96 Japanese patients with BD and 132 healthy volunteers were used. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the control group. In the B^*51 allele genotyping, 56 of 57 B51-positive patients were defined as B^*5101 and the remaining one was B^*5102.In contrast, all of 18 B51-positive normal controls were B^*5101. None of the Japanese patients and controls carried HLA-B^*5108 allele. This study revealed that B^*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of HLA-B51 antigen in Japanese BD patient group was caused by the increase of HLA-B^*5101 allele. Less

白塞病（BD）与人类白细胞抗原（HLA）B51密切相关。对希腊BD患者进行HLA-B 51等位基因分型，以研究B^*5101-B^*5107等位基因在该希腊人群中的分布。发现与BD强烈相关的B51抗原主要由等位基因B^*5101编码。由于目前已知B51抗原可由21个等位基因编码，B^*5101-B^*5121，我们对58名希腊BD患者进行了HLA- B^*5101等位基因分型。在血清学HLA分型后，使用聚合酶链反应-测序分型（PCR-SBT）方法进行HLA-B^*5101等位基因分型。发现患者组中B51抗原的频率显著高于对照组。在B51等位基因分型中，44例B51阳性患者中有34例携带B^*5101，13例携带B^*5108。与此相反，所有9例B51阳性正常对照均携带B^* ...更多信息 5101.该研究揭示了希腊人与BD的强关联，其中B^*5101和B^*5108两者。发现在意大利和沙特阿拉伯人群的患者组中，HLA-B ^*5101和HLA-B^*5108增加。我们用PCR-SBT方法进行HLA-B^*51等位基因分型，以研究是否有一个特定的B51相关等位基因与日本BD的任何相关性。使用了96名日本BD患者和132名健康志愿者。结果，证实与对照组相比，患者组中B51抗原的表型频率显著增加。在B^*51等位基因分型中，57例B51阳性患者中有56例为B^*5101，1例为B^* 5102，而18例B51阳性的正常对照均为B^*5101。日本患者和对照组均未携带HLA-B^*5108等位基因。本研究揭示了B^*51等位基因在日本人群中的分布与意大利和沙特阿拉伯人群中的分布不同，日本BD患者组中HLA-B 51抗原的显著高发生率是由于HLA-B^*5101等位基因的增加所致。少

项目成果

Mizuki N, Yabuki K, Ota M, Verity D, Katsuyama Y, Ando H, Goto K, Nomura E, Imagawa Y, Madanat W, Fayyad F, Stanford M, Ohno S, Inoko H: "Microsatellite mapping of a susceptibility locus within the HLA region for Behcet's disease using Jordanian patients"

Mizuki N、Yabuki K、Ota M、Verity D、Katsuyama Y、Ando H、Goto K、Nomura E、Imakawa Y、Madanat W、Fayyad F、Stanford M、Ohno S、Inoko H：“内敏感位点的微卫星图谱

Kitaichi N, Kotake S, Morohashi T, Onoe K, Ohao S: "Diminution of experimental autoimmune uveoretinitis(EAU) in mice depleted of NK cells"J Leukoc Biol. 72. 1117-1121 (2002)

Kitaichi N、Kotake S、Morohashi T、Onoe K、Ohao S：“NK 细胞耗尽的小鼠中实验性自身免疫性葡萄膜视网膜炎 (EAU) 的减少”J Leukoc Biol。

Imai Y.: "Cytokine production and helper T cell subsets in Vogt-Koyanagi-Harada's disease"Current Eye Research. 22. 312-318 (2001)

Imai Y.：“Vogt-Koyanagi-Harada 病中的细胞因子产生和辅助 T 细胞亚群”当前眼科研究。

Mizuki N.: "Localization of the pathojenic gene of Behcet's disease onto the HLA-B locus by polymorphism in three different populations."Invest Ophthalmol Visual Sci. 41. 3702-3708 (2000)

Mizuki N.：“通过三个不同人群的多态性将白塞氏病的致病基因定位到 HLA-B 基因座上。” 投资眼科视觉科学。

Mizuki N.: "HLA class 1 genotyping including HLA-B^*51 allele typing in the Iranian patients with Behcet's disease."Tissue Antigens. (in press).

Mizuki N.：“伊朗白塞氏病患者的 HLA 1 类基因分型，包括 HLA-B^*51 等位基因分型。”组织抗原。