Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects
Pimentel-Santos, F. M., Ligeiro, D., Matos, M., Mourão, A. F., Costa, J., Santos, H., Barcelos, A., Godinho, F., Pinto, P., Cruz, M., Fonseca, J. E., Guedes-Pinto, H., Branco, J. C., Brown, Matthew A, & Thomas, G. P. (2010) Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects. Arthritis Research and Therapy, 13(2).
A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.
A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).
A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.
We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.
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|Item Type:||Journal Article|
|Additional Information:||No file attached.|
|Keywords:||allograft inflammatory factor 1, beta7 integrin, calgranulin A, chemokine receptor CX3CR1, complementary DNA, DNA methyltransferase 1, E1A associated p300 protein, high mobility group B2 protein, kruppel like factor 5, minichromosome maintenance protein 3, osteonectin, protein tyrosine phosphatase, protein tyrosine phosphatase 1B, xeroderma pigmentosum group C protein, ankylosing spondylitis, article, ATG3 gene, BCL11B gene, blood analysis, bone metabolism, cartilage, CCDC72 gene, CHMP5 gene, CIP29 gene, Clec4d gene, CLSTN1 gene, CMTM2 gene, cohort analysis, controlled study, DGKQ gene, disease course, DNA microarray, DOCK10 gene, gene, gene expression profiling, genetic association, GMFG gene, GNG11 gene, GZMM gene, human, IL27RA gene, LSM3 gene, major clinical study, MAPK8IP3 gene, microarray analysis, MRPS18C gene, MYL6 gene, NDUFB3 gene, NDUFS4 gene, NGFRAP1 gene, PDCD10 gene, polymerase chain reaction, PPP2R1A gene, PPP2R3C gene, PSMA4 gene, receptor down regulation, receptor upregulation, SBK1 gene, SF3B14 gene, SHFM1 gene, SYF2 gene, UBL5 gene, UQCRB gene, VAMP5 gene, ZMAT2 gene, adult, cluster analysis, female, genetics, inflammation, male, middle aged, pathology, reverse transcription polymerase chain reaction, Genome-Wide Association Study, Humans, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Spondylitis, Ankylosing, Young Adult|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
|Deposited On:||29 Sep 2015 04:12|
|Last Modified:||16 Feb 2016 01:17|
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