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银屑病 MHC 基因座回归分析鉴定出与白癜风共享的遗传变异。

Psoriasis regression analysis of MHC loci identifies shared genetic variants with vitiligo.

机构信息

Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China.

出版信息

PLoS One. 2011;6(11):e23089. doi: 10.1371/journal.pone.0023089. Epub 2011 Nov 18.

Abstract

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders.

摘要

银屑病是一种常见的炎症性皮肤病,其免疫系统和表皮均具有遗传成分。PSOR1 基因座(6q21)与银屑病强烈相关;然而,由于 MHC 区域存在强烈的连锁不平衡,因此很难识别其他独立的关联。我们对 1139 例银屑病患者和 1132 例汉族对照的 MHC 区域中的 3000 多个 SNP 进行了逐步回归分析,这些 SNP 是使用 Human 610-Quad(Illumina)进行基因分型的。我们通过四个回归模型发现,HLA-C/HLA-B 中的两个 SNP(rs9468925)和 HLA-DQA2 中的 rs2858881 在所有模型中均被反复选择,这表明 PSOR1 基因座之外的多个位点与银屑病有关。更重要的是,我们发现 HLA-C/HLA-B 中的 rs9468925 与银屑病和白癜风均有关,这首次提供了重要证据表明两种主要皮肤病在 MHC 中有共同的遗传位点,并为阐明皮肤疾病的分子机制提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c2/3220662/ee819b50df60/pone.0023089.g001.jpg

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