Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies
Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies
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DOI：
10.1093/hmg/10.17.1793
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发表时间：
2001-08-15
影响因子：
3.5
通讯作者：
Menter, A
中科院分区：
文献类型：
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作者：
Bowcock, AM;Shannon, W;Menter, A
大约2%的高加索人患有银屑病（PS），这是一种由遗传和环境风险因素引发的慢性炎症性皮肤病。除了来自HLA I类区域的主要贡献外，PS易感性基因座已被定位于许多区域，包括1 q21、3q 21、4 qter、14 q31-q32、17 q24-q25、19p13.3和20 p。其中一些与其他自身免疫性/炎症性疾病中涉及的基因座重叠。全球基因表达研究开始为这些和其他复杂疾病的病因学提供见解。我们使用包含约12000个已知基因的Affyssin寡核苷酸阵列，对15名银屑病患者与6名正常对照的受累和未受累皮肤中发生的转录变化进行了更全面的分析。在阵列上检测到的转录物的表达水平首先用于使用分层聚类来确定样品彼此之间的关系。该分析清楚地区分了受累的银屑病皮肤与未受累的正常皮肤。然后鉴定在相同样品中具有相似表达模式的差异表达基因簇。32个簇中的6个包含总共177个转录物，其在所涉及的银屑病皮肤与正常皮肤中差异表达。这些差异与患者的性别、年龄、皮肤部位和HLA I类状态无关。177个基因中的10个在未受累皮肤中也有差异表达，其中几个定位于先前显示的银屑病易感基因位点。
Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environmental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions including 1q21, 3q21, 4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of these overlap with loci implicated in other autoimmune/inflammatory diseases. Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucleotide arrays comprising approximately 12 000 known genes to initiate a more comprehensive analysis of the transcriptional changes that occur in involved and uninvolved skin of 15 psoriatic patients versus six normal controls. Expression levels of the transcripts detected on the arrays were first used to determine the relationship of samples to each other using hierarchical clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were differentially expressed in involved psoriatic skin versus normal skin. These differences were independent of the gender, age, skin site and HLA class I status of the patient. Ten of the 177 genes were also differentially expressed in uninvolved skin, and several mapped to regions previously shown to harbor psoriasis susceptibility loci.