Genetic and epigenetic studies of atopic dermatitis.
Genetic and epigenetic studies of atopic dermatitis.
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特应性皮炎的遗传学和表观遗传学研究
DOI：
10.1186/s13223-016-0158-5
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Leung DY
中科院分区：
文献类型：
--
作者：
Bin L;Leung DY
特应性皮炎（AD）是一种由遗传、免疫和环境因素复杂相互作用引起的慢性炎症性疾病。最近有许多发现涉及AD的遗传和表观遗传学研究。使用术语“特应性皮炎”、“关联”、“湿疹”、“基因”、“多态性”、“突变”、“变体”、“全基因组关联研究”、”微阵列“、“基因谱分析”、“RNA测序”、“表观遗传学”和“microRNA”进行了2009年6月至2016年6月的回顾性PubMed检索。共识别出132篇英文出版物。为了阐明AD发病机制的遗传因素，在此期间进行了候选基因关联研究、全基因组关联研究（GWAS）和转录组学分析。AD发展的表观遗传机制，包括基因组DNA修饰和微小RNA转录后调节，已被探索。迄今为止，候选基因关联研究表明，聚丝蛋白（FLG）无效基因突变是AD最重要的已知风险因素，2型T辅助淋巴细胞（Th 2）信号通路中的基因是AD的第二个复制遗传风险因素。GWAS研究发现了34个AD的危险基因座，这些基因座也提示免疫反应和表皮皮肤屏障功能的基因与AD相关。此外，基因谱分析表明AD与表皮分化复合物基因表达降低和Th 2和Th 17基因升高相关。据报道，AD中TSLP和FCER 1G的低甲基化;并且发现靶向免疫抑制因子CTLA-4的miR-155在AD皮肤病变中的浸润T细胞中显著过表达。结果表明，两个主要的生物学途径负责AD病因：皮肤上皮功能和先天/适应性免疫反应。功能失调的表皮屏障和免疫反应相互影响，从而驱动AD的发展。本文的在线版本（doi：10.1186/s13223-016-0158-5）包含补充材料，可供授权用户使用。
Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms “atopic dermatitis”, “association”, “eczema”, “gene”, “polymorphism”, “mutation”, “variant”, “genome wide association study”, “microarray” “gene profiling”, “RNA sequencing”, “epigenetics” and “microRNA”. A total of 132 publications in English were identified. To elucidate the genetic factors for AD pathogenesis, candidate gene association studies, genome-wide association studies (GWAS) and transcriptomic profiling assays have been performed in this period. Epigenetic mechanisms for AD development, including genomic DNA modification and microRNA posttranscriptional regulation, have been explored. To date, candidate gene association studies indicate that filaggrin (FLG) null gene mutations are the most significant known risk factor for AD, and genes in the type 2 T helper lymphocyte (Th2) signaling pathways are the second replicated genetic risk factor for AD. GWAS studies identified 34 risk loci for AD, these loci also suggest that genes in immune responses and epidermal skin barrier functions are associated with AD. Additionally, gene profiling assays demonstrated AD is associated with decreased gene expression of epidermal differentiation complex genes and elevated Th2 and Th17 genes. Hypomethylation of TSLP and FCER1G in AD were reported; and miR-155, which target the immune suppressor CTLA-4, was found to be significantly over-expressed in infiltrating T cells in AD skin lesions. The results suggest that two major biologic pathways are responsible for AD etiology: skin epithelial function and innate/adaptive immune responses. The dysfunctional epidermal barrier and immune responses reciprocally affect each other, and thereby drive development of AD. The online version of this article (doi:10.1186/s13223-016-0158-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1084/jem.20082242
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Briot A;Deraison C;Lacroix M;Bonnart C;Robin A;Besson C;Dubus P;Hovnanian A
通讯作者：
Hovnanian A
影响因子：
14.2
作者：
De Benedetto, Anna;Rafaels, Nicholas M;McGirt, Laura Y;Ivanov, Andrei I;Georas, Steve N;Cheadle, Chris;Berger, Alan E;Zhang, Kunzhong;Vidyasagar, Sadasivan;Yoshida, Takeshi;Boguniewicz, Mark;Hata, Tissa;Schneider, Lynda C;Hanifin, Jon M;Gallo, Richard L;Novak, Natalija;Weidinger, Stephan;Beaty, Terri H;Leung, Donald Y M;Barnes, Kathleen C;Beck, Lisa A
通讯作者：
Beck, Lisa A
影响因子：
3.6
作者：
Arai, Iwao;Tsuji, Minoru;Saito, Saburo
通讯作者：
Saito, Saburo
影响因子：
12.4
作者：
Casaca, V. I.;Illi, S.;Schaub, B.
通讯作者：
Schaub, B.
影响因子：
14.2
作者：
Bin, Lianghua;Edwards, Michael G.;Heiser, Ryan;Streib, Joanne E.;Richers, Brittany;Hall, Clifton F.;Leung, Donald Y. M.
通讯作者：
Leung, Donald Y. M.