Table 2 Eleven genetic variants in NLRP3, CARD8, DAPK1, TXNIP, TLR2, P2XR7, MYD88 and CD14 were selected from the literature
SNP (gene) | Functional information | Association with auto-inflammatory phenotype |
|---|---|---|
rs10754558 (NLRP3) NLRP3 is a component of the NALP3 inflammasome. | Variant influences transcription (G > C) [46] | None |
rs35829419 (NLRP3) | Gain-of-function, with CARD8pC10X identified in arthritic patient with abnormally high IL-1 [47, 48] | Minor allele protective against celiac disease in a small study [49] |
rs7512998 (NLRP3) | None | Refer endnote 1 [20] |
rs2043211 (CARD8). CARD8 is a negative regulator of IL-1β secretion | C10X encodes a truncated protein that does not abrogate NFkB transcription [50]. Can be evaded by alternative splicing [51]. Identified as F102I in dbSNP | Interacts with NLRP3 rs35892419 in risk of Crohn’s disease [31]. Associated with disease severity in RA [50] |
rs1143623 (IL1B). IL-1β is a pro-inflammatory cytokine produced by activated NALP3 inflammasome | Promoter variant influences IL6 levels after fatty-acid rich meals [38] and IL-1β levels in small Crohn’s disease study [52] | G allele associated with protection from RA [53] |
rs4696480 (TLR2). Toll-like receptor involved in NALP3 inflammasome activation | Within binding site for the THP-1-derived nuclear protein, influences reporter expression [54] | None |
rs2569190 (CD14). CD14 is an adaptor molecule used by TLR2 | On meta-analysis is associated with Crohn’s disease [55] and asthma [56] | |
rs6853 (MYD88). MYD88 is a transducer in the TLR signalling pathway | A allele creates potential miR-562b binding site [57] | None |
rs17525809 (P2RX7). Purine receptor involved in a pathway of NALP3 activation via amyloid A | Missense variant (Val > Ala), T allele reduces activity [58] | None |
rs4878104 (DAPK1). DAPK1 (death associated kinase) is involved in NALP3 assembly. | Exhibits allelic specific differences in expression [59] | None |
rs7212 (TXNIP). TXNIP is thioredoxin-interacting protein required for full inflammasome activation | Increased mRNA expression in smooth muscle cells with G allele [60] | None |