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Table 3 Differential expression of genes associated with human arthritis in GWAS studies

From: Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis

Gene symbol Ctrl a 0 to 3d vs. Ctrl b 1 to 2w vs. Ctrl c 3 to 4w vs. Ctrl d Decline vs. Ctrl e Protein function
  log2 Fold change ( P -value)  
Ankylosing spondylitis
Hapln1 6.72 1.69 (0.15) 3.10 (0.01) 2.89 (0.005) 2.08 (0.01) Involved in cartilage development and bone formation. Associated with osteophyte formation in OA [ 30 ].
Edil3 5.58 1.53 (0.14) 2.95 (0.003) 3.07 (0.005) 2.33 (0.11) Integrin ligand with a proposed role in cartilage development and angiogenesis. Inhibitor of the WNT pathway [ 30 ].
Ano6 7.22 2.25 (0.05) 1.88 (0.04) 1.61 (0.14) 1.19 (0.60) Regulates phosphatidylserine exposure on the cell surface, which is essential for mineralisation of bone and involved in osteoclast formation [ 30 , 31 ].
Psmg1 6.95 2.04 (0.002) 1.91 (0.002) 1.37 (0.03) 1.03 (0.78) Proteasome Assembly Chaperone 1. The gene is, in addition, associated with inflammatory bowel disease [32].
Rheumatoid arthritis
Anapc4 6.85 1.77 (0.0008) 1.91 (0.0003) 1.45 (0.02) 1.18 (0.45) An SNP close to this gene was associated with RA susceptibility [33]. The encoded protein is an E3 ubiquitin ligase involved in control of the cell cycle, muscle cell function, and function of neurons [34].
Cd84 5.61 3.07 (0.01) 3.01 (0.004) 2.17 (0.02) 1.51 (0.12) Membrane protein involved in immune function. High expression of the gene was associated with a positive response to Etanercept treatment [35].
Il6st 9.44 2.41 (0.03) 1.79 (0.06) 1.52 (0.10) 1.09 (0.76) Signal transducing subunit for cytokines belonging to the IL-6 family. Activates Stat-3, which plays a role in OC and OB differentiation and their interaction [ 36 ].
Ptpn2 6.68 1.74 (0.06) 1.78 (0.02) 1.32 (0.30) 1.46 (0.16) Protein phosphatase involved in T-cell activation by regulation of the JAK/STAT signalling pathway [33,37,38].
Cdk6 5.88 2.51 (0.10) 2.35 (0.08) 2.11 (0.08) 1.64 (0.21) Cyclin-dependent kinase involved in proliferation of lymphocytes [39].
Prkcq 7.42 0.48 (0.17) 0.65 (0.26) 0.55 (0.16) 0.61 (0.32) Kinase involved in activation of NFκB and AP-1 transcription factors [39].
Prkch 7.20 1.36 (0.04) 1.43 (0.07) 1.58 (0.06) 0.99 (0.95) Serine/threonine kinase. The association with RA is suggestive [38].
Osteoarthritis
Gnl3 7.81 2.41 (0.11) 2.10 (0.08) 2.17 (0.07) 1.47 (0.34) Nucleostemin. Increased in in vitro cultures of chondrocytes from patients with OA [40].
Glt8d 7.18 1.97 (0.03) 1.99 (0.02) 1.43 (0.05) 1.13 (0.71) Involved in glycosylation of cartilage proteins [40].
Pla2g 5.96 1.47 (0.16) 1.67 (0.04) 2.06 (0.03) 1.71 (0.04) Cytosolic phospholipase A2 enzyme. mRNA transcript was abundantly expressed in chondrocytes from OA patients [41].
Ptgs2 6.91 2.66 (0.01) 1.72 (0.07) 1.15 (0.41) 1.56 (0.03) Cyclooxygenase 2 (COX-2). mRNA transcript was abundantly expressed in chondrocytes from OA patients [41].
Col12a1 8.24 4.56 (0.04) 4.82 (0.01) 2.97 (0.04) 1.74 (0.22) A SNP close to this gene has been associated with OA susceptibility [ 40 ]. The encoded protein is expressed by OB in areas of bone formation. KO mice have skeletal abnormalities with less mechanical strength and reduced matrix deposition [ 24 ].
  1. aMean log2 expression in non-induced control mice. Mean fold change and P-value in comparison to control: bon day 0 to 3, cin week 1 to 2, din week 3 to 4, ein the declining disease phase. Genes shown in bold are encoding proteins with a known function in cartilage- or bone remodelling. Ctrl, control; GWAS, genome-wide association studies; IL-6, interleukin 6; KO, knockout; NFκB, nuclear factor kappa B; OA, osteoarthritis; OB, osteoblast; OC, osteoclast; RA, rheumatoid arthritis; WNT, wingless-type.