title: Genes expressed in blood link osteoarthritis with apoptotic pathways.
abstract: OBJECTIVE
  To identify novel gene expression networks in blood of osteoarthritis patients compared to controls.
  
  
  METHODS
  A comprehensive exploration of gene expression in peripheral blood was performed by microarray analysis for a subset of osteoarthritis patients from the Genetics osteoARthritis and Progression (GARP) study in comparison with sex and age-matched healthy controls. To identify pathways, we performed gene enrichment analyses (database for annotation, visualisation and integrated discovery and search tool for the retrieval of interacting genes). Quantitative PCR analysis in overlapping and in additional osteoarthritis samples was performed for prioritised genes to validate and replicate findings. Classification of cases and controls was explored by applying statistical models.
  
  
  RESULTS
  741 probes representing 694 unique genes were differentially expressed between cases and controls, including 86 genes expressed with at least a 1.5-fold difference. ATF4, GPR18 and H3F3B were among the top genes identified (p<4.5 × 10(-8)). We found that in the blood of osteoarthritis patients the apoptosis pathway, including the well-known gene CASP3, was significantly enriched among the differentially expressed genes. Our findings were validated in independent samples and when using a small subset of the validated genes, we could accurately distinguish patients from controls (area under the curve 98%).
  
  
  CONCLUSIONS
  In the current study, we have identified specific gene expression networks, in the easily accessible tissue blood, which associated consistently with osteoarthritis among GARP study cases. Our data further hint at the relevance of apoptosis as an aetiological factor in osteoarthritis onset, thereby qualifying expression profiling of blood as a useful tool to understand the underlying molecular mechanisms of osteoarthritis.
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Yolande F M
authors.initials: YF
authors.lastname: Ramos
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors.forename: Steffan D
authors.initials: SD
authors.lastname: Bos
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Lakenberg
authors.affiliation: Department of Biostatistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Böhringer
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: den Hollander
authors.affiliation: Departments of Clinical Epidemiology and Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: Kloppenburg
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010003:Osteoarthritis / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D001798:Blood Proteins
keywords: Epidemiology; Osteoarthritis; Outcomes research