Analysis of HLA-B27, investigating of the susceptibility of AS and AAU

HLA-B27分析，AS、AAU易感性调查

• 批准号: 07671903
• 负责人: JOKO Satoru
• 金额: $ 1.54万
• 依托单位: Saitama Medical School (1996)The University of Tokyo (1995)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671903/
• 关键词: HLA-B27; Ankylosing Spondylitis; Acute anterior uveitis; Haplotype; HLA; 前部ぶどう膜炎; 対立遺伝子

The strong association between Ankylosing Spondylitis (AS) and HLA-B27 has been reported from many countries, but, very rare from Japan, because AS as well as the frequency of HLA-B27 is rare in Japan as compared with Caucasians. HLA-B27 is also known to be associated with acute anterior uveitis (AAU) which is often complicated with AS.We investigated 46 Japanese patients with AS and 59 with AAU ; 24 patients with AS and AAU,a total number of 81 patients, of which 44 patients carried HLA-B27. PCR-SSCP was employed for B27 DNA subtyping, and the amino acid sequence was confirmed by automated sequencer. We also performed class II DNA typing using PCR-SSCP and-RFLP method. We estimated the linkage disequilibrium between each subtype of HLA-B27 and class II alleles (DR,DQ locus). We found two subtypes of HLA-B27, B^<**>2704 and B^<**>2705. The former was found in 34 (77.3%) patients and the latter in 10 (22.7%). We could not find any differences in the frequencies of 2 HLA-B27 subtypes among AS patients, AAU patients and B27 positive controls. Then AS patients were divided into two groups ; with AAU and without AAU.The frequencies of B27 subtypes were almost equal between the two groups, however, we found a significant difference in the frequency of HLA-DR8, which was increased in the patients with AAU (p<0.0005). This result may suggest that the susceptibility of AAU in the AS patients is influenced by HLA-DR8. HLA-B27 containing HLA-A,B,DR haplotypes frequencies are now being investigated.

强直性脊柱炎（AS）与HLA-B27之间的密切关系在许多国家都有报道，但在日本非常罕见，因为与高加索人相比，AS和HLA-B27的发病率在日本很少见。HLA-B27也被认为与急性前葡萄膜炎（AAU）有关，后者常并发AS。我们调查了46名日本AS患者和59名AAU患者；AS合并AAU患者24例，共81例，其中携带HLA-B27患者44例。采用PCR-SSCP进行B27 DNA分型，并用自动测序仪确定氨基酸序列。我们还使用PCR-SSCP和rflp方法进行了II类DNA分型。我们估计了HLA-B27各亚型与II类等位基因（DR，DQ位点）之间的连锁不平衡。我们发现了HLA-B27的两个亚型，B^<**>2704和B^<**>2705。前者34例（77.3%），后者10例（22.7%）。我们没有发现AS患者、AAU患者和B27阳性对照中2种HLA-B27亚型的频率有任何差异。然后将AS患者分为两组；有AAU和没有AAU。B27亚型的频率在两组之间几乎相等，但我们发现HLA-DR8的频率在AAU患者中有显著差异（p<0.0005）。提示AS患者对AAU的易感性受HLA-DR8的影响。目前正在调查含有HLA-A、B、DR单倍型的HLA-B27的频率。

项目成果

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Yasuhiro Konno：“强直性脊柱炎患者的急性前葡萄膜炎、HLA-B27 亚型和 DR8”临床风湿病学特别版，第 8 卷/第 3 期（1997 年）。

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Satoshi Joko：“根据 WHO-MDT 分类的麻风病（汉森病）类型和 HLA 类 II 等位基因”，日本汉森病学会杂志 65(2)（1996 年）。

Y.Konno, et al: "Human leukocyte antigens and sex distributions in ocular sarcoidosis" Rinsho Ganka (Jpn J Clin Ophthalmol). 50 (6). 1140-1144 (1996)

Y.Konno 等人：“眼结节病中的人类白细胞抗原和性别分布”Rinsho Ganka（Jpn J Clin Ophasemol）。