title: Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects.
abstract: BACKGROUND
  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.
authors.affiliation: CEDOC, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Campo dos Mártires da Pátria, n° 130, 1169-056 Lisboa, Portugal. pimentel.santos@gmail.com
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Pimentel-Santos
authors.forename: Dário
authors.initials: D
authors.lastname: Ligeiro
authors.forename: Mafalda
authors.initials: M
authors.lastname: Matos
authors.forename: Ana F
authors.initials: AF
authors.lastname: Mourão
authors.forename: José
authors.initials: J
authors.lastname: Costa
authors.forename: Helena
authors.initials: H
authors.lastname: Santos
authors.forename: Anabela
authors.initials: A
authors.lastname: Barcelos
authors.forename: Fátima
authors.initials: F
authors.lastname: Godinho
authors.forename: Patricia
authors.initials: P
authors.lastname: Pinto
authors.forename: Margarida
authors.initials: M
authors.lastname: Cruz
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
authors.forename: Henrique
authors.initials: H
authors.lastname: Guedes-Pinto
authors.forename: Jaime C
authors.initials: JC
authors.lastname: Branco
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Gethin P
authors.initials: GP
authors.lastname: Thomas
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000473:pathology; D055815:Young Adult