Table 2 Biological interpretation of the single nucleotide polymorphisms (SNPs) associated with ankylosing spondylitis (AS)
Gene | Rs-number | Pathway | Model | OR (95% CI) | P-value / Bonferronia | Effect of minor-allele | Biological interpretation |
|---|---|---|---|---|---|---|---|
TLR1 | rs4833095 | Pathogen recognition | CC vs TT | 2.59 (1.48–4.51) | 0.00081 / 0.04 | 743C increase TLR1 level in PBMC [56] | Increased TLR1 level was associated with increased risk of AS. This could indicate that a genetically determined high activity of the NFkB pathway, and thus high TNF-α and IL-17 activity, was associated with increased risk of AS. |
TLR4 | rs1554973 | Pathogen recognition | CC vs TT | 0.55 (0.34–0.86) | 0.010 / 0.51 | Unknown [67] | – |
LY96 | rs11465996 | Pathogen recognition | GG vs CC | 0.68 (0.46–1.00) | 0.049 / 1.00 | -1625G increase MD-2 and TNF-α levels in human U937 cells and whole blood leukocytes [57] | Increased MD-2 and TNF-α level was associated with a reduced risk of AS. In contrast to the other results this indicate that genetically determined high TNF-driven inflammatory response was associated with reduced risk of AS. |
TNF | rs1800629 | Cytokines | GA or AA vs GG | 0.56 (0.44–0.72) | 0.0000047 / 0.00024 | -308A increase expression in jurkat cells [65], reduce mRNA level in PBMC and serum [48] or no association was found [49] | Reduced TNF-α mRNA level was associated with reduced risk of AS. This could indicate that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
TNF | rs361525 | Cytokines | GA or AA vs GG | 0.49 (0.31–0.78) | 0.0024 / 0.12 | -238A reduce expression in PBMC [49] | Reduced TNF-α expression was associated with reduced risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
TNFRSF1A | rs4149570 | Cytokines | GT or TT vs GG | 1.44 (1.15–1.80) | 0.0013 / 0.066b | -609 T increase expression in PBMC [50] | Increased TNF-α receptor 1 expression was associated with increased risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
PTPN22 | rs2476601 | Immune response | GA or AA vs GG | 0.76 (0.58–0.98) | 0.037 / 1.00 | 1858A reduce TNF-α level in serum [51] | Reduced TNF-α level was associated with reduced risk of AS. This indicates that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS. |
IL18 | rs187238 | Cytokines | GC or CC vs GG | 0.80 (0.65–0.99) | 0.044 / 1.00 | -137C reduce IL-18 level in serum [53] and expression in PBMC [54] | Reduced IL-18 expression, and thus reduced IL-17 and TNF-α activity, was associated with reduced risk of AS. This indicates that a genetically determined high activity of the IL23/IL17 pathway was associated with increased risk of AS. |
IL23R | rs11209026 | Cytokines | GA or AA vs GG | 0.60 (0.42–0.87) | 0.0071 / 0.36 | rs11209026A reduce IL-17 level in PBMC [52] | Reduced IL-17 level was associated with reduced risk of AS. This indicates that a genetically determined high activity of the IL23/IL17 pathway was associated with increased risk of AS. |