Genomic analysis and identification of susceptible genes for alopecia areata

斑秃易感基因的基因组分析及鉴定

• 批准号: 22591229
• 负责人: IKEDA Shigaku
• 金额: $ 2.91万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591229/
• 关键词: 円形脱毛症; ゲノム解析; マイクロサテライト; SNP; 遺伝子; HLA; 疾患感受性遺伝子; ゲノム相関解析; HLA領域

In this study, we have identified a strong candidate region for alopecia areata on chromosome 6, at around HLA-B locus (OR: 3.21). By detailed genetic analysis of this region using microsatellite markers and SNPs, we could successfully narrow the region to 2 megabase interval (Haida Y, Ikeda S, et al: An association study of Alopecia Areata within the HLA region using microsatellite markers. Immunogenetics, 2013; 65: 553-7.）. We further sequenced this 2 megabase region on 50 alopecia areata cases, and identified a strongly associated haplotype for alopecia areata (OR: 3.75). Moreover, in this region, we have identified multiple mutations and/or polymorphisms in the exons and introns of a gene, that frequently resulted in the formation of stop codon mutations and truncation of gene products. These results indicated that this gene could be a strong susceptible gene for alopecia areata. We are now producing gene modified mice for this gene, and also examining the expression of this candidate gene on the alopecia areata patients’ skin.

在本研究中，我们确定了斑秃的一个强有力的候选区域6号染色体上，在HLA-B位点附近（OR：3.21）。通过使用微卫星标记和SNP对该区域进行详细的遗传分析，我们可以成功地将该区域缩小到2兆碱基间隔（Haida Y，Ikeda S，et al：An association study of Alopecia Areata within the HLA region using microsatellite marker. Immunogenetics，2013; 65：553-7.）。我们进一步对50例斑秃病例的这2兆碱基区域进行了测序，并确定了与斑秃强相关的单倍型（OR：3.75）。此外，在该区域中，我们已经鉴定了基因的外显子和内含子中的多个突变和/或多态性，其经常导致终止密码子突变和基因产物截短的形成。这些结果表明该基因可能是斑秃的一个强易感基因。我们现在正在生产这种基因的基因修饰小鼠，并检查这种候选基因在斑秃患者皮肤上的表达。

项目成果

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• 期刊: J Dermatol Sci
• 影响因子: 4.6
• 作者: Aung G;Niyonsaba F;et al
• 通讯作者: et al