Table 2.
Primary Sjögren’s syndrome risk loci derived from candidate gene studies
| Gene | SNP | ORa (95% CI) | P-value | Function | References |
|---|---|---|---|---|---|
| IRF5-TNPO3 | rs2004640 | 1.93 (1.15, 3.42) | 0.01 | Type I IFN and TLR signalling, cytokine production (e.g. IL-6, IL-12), apoptosis | Miceli-Richard et al. [25] |
| rs10488631 | 1.57 (1.23, 1.99) | 3.23E-04 | Nordmark et al. [26] | ||
| CGGGGindel | 2.00 (1.50, 2.70) | 6.60E-06 | Miceli-Richard et al. [27] | ||
| 1.49 (1.24, 1.79) | 2.41E-05 | Nordmark et al. [26] | |||
| rs13246321 | 1.70 (1.35, 2.13) | 5.50E-06 | Nordmark et al. [28] | ||
| STAT4 | rs7574865 | 1.46 (1.09, 1.97) | 0.01 | Type I and II IFN pathways, NOD2 signalling | Korman et al. [29] |
| 1.40 (1.21, 1.62) | 4.70E-06 | Palomino-Morales et al. [30] | |||
| rs7582694 | 1.41 (1.14, 1.73) | 1.45E-03 | Nordmark et al. [26] | ||
| 1.40 (1.15, 1.70) | 7.00E-04 | Nordmark et al. [28] | |||
| BLK-FAM167A | rs12549796 | 1.37 (1.15, 1.63) | 4.70E-04 | B cell signalling and development, thymopoiesis, insulin secretion and synthesis, NF-κB signalling | Nordmark et al. [28] |
| EBF1 | rs3843489 | 1.68 (1.29, 2.18) | 9.90E-05 | Enhancer of transcriptional activity during B cell development | Nordmark et al. [28] |
| TNSF4/OX40L | rs1234315 | 1.34 (1.14, 1.64) | 7.40E-04 | Co-stimulation, T cell proliferation, cytokine production | Nordmark et al. [28] |
| BAFF/TNFSF13B | 5′ haplotypeb | 2.60 (1.70, 4.10) | 4.00E-05 | B cell maturation, proliferation and survival, epithelial cell survival | Nossent et al. [31] |
| 5′ haplotypec (TATT, GTTC) | – | <0.05 | Nezos et al. [32] | ||
| NCR3/NKp30 | rs11575837 | 0.48 | 0.0039 | Regulation of dendritic and NK cell communication, regulation of Th1 (IL-12 and IFN-γ) cytokines | Rusakiewicz et al. [33] |
| rs2736191 | 0.56 | 0.0019 | Rusakiewicz et al. [33] | ||
| PTPN22 | rs2476601 | 2.42 (1.24, 4.75) | 0.01 | T cell activation | Gomez et al. [34] |
| TNIP1 | rs3792783 | 1.33 (1.16, 1.52) | 3.40E-05 | NF-κB signalling, EGF/ERK signalling, TNF-induced apoptosis | Nordmark et al. [35] |
| rs7708392 | 1.21 (1.08, 1.36) | 1.30E-03 | Nordmark et al. [35] | ||
| TNFAIP3 | rs2230926 | 3.26 (1.31, 8.12) | 0.011 | NF-κB signalling (repressor), TNF-induced apoptosis, TLR4 signalling, cytokine production (e.g. IL-1B) | Nocturne et al. [36] |
| BAFF-R | His159Tyr | 4.13 (1.19, 14.3) | 0.01 | NF-κB2 signalling | Papageorgiou et al. [37] |
| LTA/LTB/TNF | rs1800629 | 2.00 (1.61, 2.49) | 2.48E-10 | Lymphoid organogenesis, tertiary lymphoid tissue maintenance | Bolstad et al. [38] |
| rs909253 | 1.59 (1.34, 1.89) | 1.25E-07 | |||
| MECP2 | rs17435 | 1.33 (1.12, 1.59) | 0.0016 | Methylation-mediated transcriptional silencing | Cobb et al. [39] |
| CHRM3 | rs7548522 | 1.93 (1.24, 3.01) | 0.0033 | Muscarinic receptor | Appel et al. [40] |
a
The OR for each variant indicates the disease risk conferred by the minor allele.
b
The haplotype in the 5′ regulatory region of the BAFF gene is constituted by the SNPs rs9514827:-2841T>C, rs3759467:-2704T>C, rs1041569:-2701T>A and rs9514828:871C>T.
c
Nezos et al. [32] analysed the 5′ regulatory region BAFF haplotype and also identified risk haplotypes for lymphoma.
EGF/ERK: epidermal growth factor/extracellular signal-regulated kinase; NOD2: nitric oxide synthetase 2.