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Table 1 Genes and gene polymorphisms linked with axSpA

From: Targeting inflammatory pathways in axial spondyloarthritis

Gene Name Pathway and/or putative function References
Genes and gene polymorphisms
HLA-B27
B2702, 2703, 2704, 2705, 2707, 2708, 2710, 2714, 2715, 2719; 2706 and 2709 (reduced risk)
Human leukocyte antigen B27
105 subtypes encoded by 132 alleles; numerous genetic risk variants
Peptide presentation to T cells, HLA-B27 molecule misfolding leading to endoplasmic reticulum stress reaction, homodimer formation leading to natural killer (NK) cell activation Interacts with ERAP1 Caffrey 1973 [141]
Brewerton 1973 [65]
Schlosstein 1973 [66]
Montserrat 2006 [142]
Cipriani 2003 [143]
Yang 2014 [144]
Fiorillo 2003 [145]
Khan 2013 [146]
Jaakkola 2006 [147]
Armas 1999 [148]
Reveille 2006 [149]
HLA-B40, B13, B47, B51 B60, B14 Human leukocyte antigen B Antigen recognition Interacts with ERAP1 Cortes 2015 [150]
Van Gaalen 2013 [151]
Tumor necrosis factor (TNF) pathway
TNFRSF1A/TNFR1 (383 A/C, rs4149577, rs4149576, rs1860545, and rs7954567 polymorphisms) Tumor necrosis factor receptor superfamily member 1A (tumor necrosis factor receptor 1) TNF signaling
Nuclear factor (NF)-κB activation and cytokine production
Corona-Sanchez 2012 [152]
Davidson 2011 [153]
Karaderi 2012 [154]
Evans 2011 [22]
TRADD region on chromosome 16 Tumor necrosis factor receptor type 1-associated death domain TNF signaling
NF-κB activation and cell death
Pointon 2010 [155]
Hsu 1995 [156]
Interleukin 23 pathway
IL-23R (multiple polymorphisms) Interleukin-23 receptor gene
Elevated in AS gut epithelium, from CD 4, γδ T, NK, innate lymphoid, mast cells
Th17-mediated immunity
Production of IL-17A, IL-17F, IL-22, and IFN-γ
Reveille 2010 [62]
Burton 2007 [61]
Danoy 2010 [157]
Dong 2013 [158]
Cortes 2013 [159]
Di Cesare 2009 [160]
IL12B (rs6871626, rs10045431, and rs3212227 polymorphisms) Interleukin-12B Activation and differentiation of IL-23R-expressing cells Danoy 2010 [157]
Zhang 2015 [161]
Wong 2012 [162]
IL-6R (rs4129267 polymorphism) Interleukin-6R Th17-mediated immunity
TH17 cell differentiation
Reveille 2015 [75]
Cortes 2013 [159]
IL1R2 (rs2310173 polymorphism)
IL1R1-IL1R2 (rs4851529 and rs2192752 polymorphisms)
Interleukin 1 receptor, type I/II Th17-mediated immunity
Modulation of IL-1 response
Reveille 2010 [62]
Reveille 2015 [75]
JAK2 (rs10758669 polymorphism, rs1536798/rs10119004/rs7857730-CGT haplotype) Janus kinase 2 IL-23R signaling molecule Danoy 2010 [157]
Chen 2010 [163]
STAT3 (rs2293152, rs6503695, rs744166 polymorphisms) Signal transducer and activator of transcription 3 IL-23R and IL-6 signaling molecule Davidson 2011 [153]
Danoy 2010 [157]
Lymphocyte development and activation
ERAP1 (multiple polymorphisms) Endoplasmic reticulum aminopeptidase-1 Also pairs with Cw6 of psoriasis, B51 of Behcet’s, A29 of birdshot chorioretinopathy but not NOD2 of Crohn’s Puromycin-sensitive aminopeptidase Peptide presentation-Interacts with HLA-B27 and HLA-B40 Reeves 2014 [164]
Evans 2011 [22]
Abdullah 2015 [165]
Chen 2015 [166]
Bang 2011 [167]
Brown 2016 [168]
TYK2 (rs35164067, rs6511701, rs280518 polymorphisms) Tyrosine kinase 2 Signaling from cytokine receptors, including IL-23R Reveille 2015 [75]
Cortes 2013 [159]
CARD9 (rs11145835, rs10781500 polymorphisms) Caspase recruitment domain family, member 9 Development of Th17 activation to some pathogens Ma 2014 [169]
Evans 2011 [22]
RUNX3 (rs6600247 polymorphism) Runt-related transcription factor 3 Reduction in CD8 T cell counts Reveille 2015 [75]
Cortes 2013 [159]
KIR3DL1 Killer immunoglobulin-like receptor-3 DL1 Inhibits cytotoxicity of NK cells Abdullah 2015 [165]
Zvyagin 2010 [170]