Identification of psoriasis-susceptible gene

银屑病易感基因的鉴定

• 批准号: 12470520
• 负责人: TAMIYA Gen
• 金额: $ 7.68万
• 依托单位: Tokai 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 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470520/
• 关键词: microstellite marker; psoriasis valgaris; association study; SNPs; antisence RNA; RT-PCR; 転写産物; アンチセンス RNA; 相関解析; マイクロアレイ; 発現遺伝子解析; HLA

Association analysis using refined microsatellite markers has localized a susceptibility locus for psoriasis vulgaris within a 54 kb segment telomeric to the HLA-C gene. Furthermore, we have discovered novel five genes expressed in skin keratinocyte in this susceptibility locus.In order to identify exclusively susceptibility gene, we tried to discover all SNPs in this region and to analysis case-control association study. 200 gSNPs (genomic SNP) and 80 cSNPs (coding SNP) were detected by this analysis. The genes had statistically significant differentiation allele between the patients and controls were the SEKK1 and the S genes. Because the results of association study about the S gene by another groups were different from our datas, the S gene was not susceptibility gene. We estimated that the SEEK1 gene is a susceptibility gene.It is predicted that the transcript of the SEEK1 gene influences onset of psoriasis, because the SEEK1 gene may not produce the protein and is a chain of antisence aginst the S gene. Analysis of transcript of the SEEK1 gene found that the transcripts was continuous within susceptibility region, had a lot of variants and almost had chain of antisence aginst the S gene. In the future, We will demonstrate the relations with both genes, by measuring the level of expression of genes in lesional skin and normal skin.

利用精细微卫星标记进行关联分析，将寻常型银屑病的易感位点定位在54 kb的HLA-C基因片段端粒内。此外，我们还发现了在皮肤角质细胞中表达的五个新基因。为了确定唯一的易感基因，我们试图发现该区域的所有snp，并进行病例-对照关联研究。共检测到200个gsnp（基因组SNP）和80个csnp（编码SNP）。患者与对照组差异有统计学意义的等位基因为SEKK1和S基因。由于其他群体对S基因的关联研究结果与我们的数据不同，因此S基因不是易感基因。我们估计SEEK1基因是一个易感基因。预测SEEK1基因的转录影响牛皮癣的发病，因为SEEK1基因可能不产生该蛋白，并且是针对S基因的反义链。对SEEK1基因的转录本分析发现，转录本在易感区是连续的，具有大量的变异，并且几乎具有针对S基因的反义链。在未来，我们将通过测量病变皮肤和正常皮肤中基因的表达水平来证明与这两个基因的关系。

项目成果

Teraoka Y, et al: "Genetic polymorphisms in the cell growth regulated gene, SCI telomeric of the HLA-C gene and lack of association with psoriasis vulgaris"Tissue Antigens. 55. 206-211 (2000)

Teraoka Y 等人：“细胞生长调节基因的遗传多态性、HLA-C 基因的 SCI 端粒以及与寻常型银屑病缺乏关联”组织抗原。

Ota M. et al.: "On the MICA deleted-MICB null, HLA-B*4801 haplotype"Tissue Antigens. 56(3). 268-271 (2000)

Ota M. 等人：“关于 MICA 缺失-MICB 无效，HLA-B*4801 单倍型”组织抗原。

Saito S. et al.: "Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population."Tissue Antigens. 56(6). 522-529 (2000)

Saito S. 等人：“日本人群中 HLA I 类和 II 类基因座的等位基因 DNA 分型定义的等位基因频率和单倍型关联。”组织抗原。

Mizuki N, et al.: "Microstellite mapping of a susceptible locus within the HLA region for Behcet's disease using Jordanian patients"Hum Immunol. 62. 186-190 (2001)

Mizuki N 等人：“使用约旦患者对白塞氏病 HLA 区域内的易感位点进行 Microstellite 定位”HumImmunol。

Matsuzaka Y. et al.: "New polymorphic microsatellite markers in the human MHC class II region."Tissue Antigens. 56(6). 492-500 (2000)

Matsuzaka Y. 等人：“人类 MHC II 类区域中的新多态性微卫星标记。”组织抗原。