Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Pimentel-Santos, Fernando M., Ligeiro, Dário, Matos, Mafalda, Mourão, Ana F., Costa, José, Santos, Helena, Barcelos, Anabela, Godinho, Fátima, Pinto, Patricia, Cruz, Margarida, Fonseca, João E., Guedes-Pinto, Henrique, Branco, Jaime C., Brown, Matthew A. and Thomas, Gethin P. (2011) 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: R57.1-R57.8. doi:10.1186/ar3309


Author Pimentel-Santos, Fernando M.
Ligeiro, Dário
Matos, Mafalda
Mourão, Ana F.
Costa, José
Santos, Helena
Barcelos, Anabela
Godinho, Fátima
Pinto, Patricia
Cruz, Margarida
Fonseca, João E.
Guedes-Pinto, Henrique
Branco, Jaime C.
Brown, Matthew A.
Thomas, Gethin P.
Title Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects
Journal name Arthritis Research and Therapy   Check publisher's open access policy
ISSN 1465-9905
1478-6354
1478-6362
Publication date 2011-04-07
Year available 2011
Sub-type Article (original research)
DOI 10.1186/ar3309
Open Access Status DOI
Volume 13
Issue 2
Start page R57.1
End page R57.8
Total pages 8
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Abstract Introduction: 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.
Formatted abstract
Introduction: 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.

Methods: 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).

Results: 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.

Conclusions: 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.
Keyword Peripheral-blood
Interferon-gamma
T-cells
Illumina microarray
Expression profiles
Spondyloarthropathy
Susceptibility
Chondrocytes
Pathogenesis
Lymphocytes
Interferon-γ
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 28 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 14 Aug 2011, 11:10:16 EST by System User on behalf of UQ Diamantina Institute