Global transcriptional analysis of psoriatic skin and blood confirms known disease-associated pathways and highlights novel genomic "hot spots" for differentially expressed genes.

Autor: Coda AB; Division of Dermatology and Cutaneous Sciences, Center for Investigative Dermatology, Michigan State University, East Lansing, MI, USA. acoda@ucsd.edu, Icen M, Smith JR, Sinha AA
Jazyk: angličtina
Zdroj: Genomics [Genomics] 2012 Jul; Vol. 100 (1), pp. 18-26. Date of Electronic Publication: 2012 May 11.
DOI: 10.1016/j.ygeno.2012.05.004
Abstrakt: There are major gaps in our knowledge regarding the exact mechanisms and genetic basis of psoriasis. To investigate the pathogenesis of psoriasis, gene expression in 10 skin (5 lesional, 5 nonlesional) and 11 blood (6 psoriatic, 5 nonpsoriatic) samples were examined using Affymetrix HG-U95A microarrays. We detected 535 (425 upregulated, 110 downregulated) DEGs in lesional skin at 1% false discovery rate (FDR). Combining nine microarray studies comparing lesional and nonlesional psoriatic skin, 34.5% of dysregulated genes were overlapped in multiple studies. We further identified 20 skin and 2 blood associated transcriptional "hot spots" at specified genomic locations. At 5% FDR, 11.8% skin and 10.4% blood DEGs in our study mapped to one of the 12 PSORS loci. DEGs that overlap with PSORS loci may offer prioritized targets for downstream genetic fine mapping studies. Novel DEG "hot spots" may provide new targets for defining susceptibility loci in future studies.
(Copyright © 2012 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE