Genome-wide association study of recalcitrant atopic dermatitis in Korean children.
Genome-wide association study of recalcitrant atopic dermatitis in Korean children.
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DOI：
10.1016/j.jaci.2015.03.030
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Sohn MH
中科院分区：
文献类型：
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作者：
Kim KW;Myers RA;Lee JH;Igartua C;Lee KE;Kim YH;Kim EJ;Yoon D;Lee JS;Hirota T;Tamari M;Takahashi A;Kubo M;Choi JM;Kim KE;Nicolae DL;Ober C;Sohn MH
特应性皮炎（AD）是一种异质性慢性炎症性皮肤病。大多数婴儿期AD在儿童期消退，但伴有过敏性致敏的中度至重度AD更有可能持续到成年期，并且更常与其他过敏性疾病一起发生。我们试图通过在韩国儿童中进行AD的首次全基因组关联研究（GWAS）来寻找易感位点，其中韩国儿童的阿尔茨海默病被定义为中度至重度AD伴过敏性致敏。我们的研究包括246名患有过敏性AD的儿童和551名有过敏性疾病和过敏性致敏阴性史的成人对照。对来自这些个体的DNA进行基因分型;在质量控制检查后，对常见的SNP进行插补并用于GWAS。13q21.31区域的SNPs在全基因组显著性阈值（P < 2.0×10−8）下与阿尔茨海默病相关。这些相关的SNP距离最近的基因PCDH 9> 1 Mb。另外四个位点的SNP P < 1×10−6，包括NBAS（2p24.3）、THEMIS（6q22.33）、GATA 3（10 p14）和SCAPER（15q24.3）基因或其附近的SNP。对血清总IgE水平的进一步分析表明，13q21.31可能主要是一个IgE基因座，对已发表数据的分析表明，15q24.3区域的SNP是免疫细胞中两个邻近基因ISL 2和PSTPIP 1的表达数量性状基因座（eQTL）。我们对阿尔茨海默病的GWAS发现了新的易感区域，其中含有参与上皮细胞功能和免疫失调的基因，这是AD的两个关键特征，并可能扩展我们对它们在发病机制中作用的理解。
Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate to severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, defined as moderate to severe AD with allergic sensitization. Our study included 246 children with recalcitrant AD and 551 adult controls with a negative history of both allergic disease and allergic sensitization. DNA from these individuals was genotyped; sets of common SNPs were imputed and used in the GWAS after quality control checks. SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0×10−8). These associated SNPs are >1Mb from the closest gene, PCDH9. SNPs at four additional loci had P < 1×10−6, including SNPs at or near the NBAS (2p24.3), THEMIS (6q22.33), GATA3 (10p14) and SCAPER (15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 may be primarily an IgE locus, and analyses of published data demonstrated SNPs at the 15q24.3 region are expression quantitative trait loci (eQTL) for two nearby genes, ISL2 and PSTPIP1, in immune cells. Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, two key features of AD, and potentially extend our understanding of their role in pathogenesis.