Gene (locus link id) | Gene Function | Polymorphisms | MAF | Reference and previous association |
---|---|---|---|---|
CRP 1q21-q23 (1401) | Activates the classical pathway of complement. SNP2 alters basal levels of CRP. SNP4 has been associated with SLE and antinuclear autoantibody production. A polymorphic GT repeat in CRP has been associated with SLE. | SNP2 (rs1800947) SNP4 (rs1205) Microsatellite (ss28514831) | 0.07 & 0.33 respectively, Caucasian parental. GT16 & GT21, 0.62 and 0.24, respectively, Caucasian controls. | SLE: Microsatellite P = 0.007, SNP4 P = 0.0008; 586 families [14]. Microsatellite [15]. |
FCRL3 1q21-q22 (115352) | FCRL3, a member of the Fc receptor-like family, polymorphism alters the binding affinity of nuclear factor κB and regulates FCRL3 expression. Associated with RA, SLE and autoimmune thyroid disease (GD and HT) | Fcrl3_3 (rs7528684) | 0.37 Japanese controls | RA: P = 8.5 × 10-7, OR = 2.15 (95% CI = 1.58–2.93) 830 cases and 658 controls. SLE: P = 0.0017, OR = 1.49 (95% CI = 1.16–1.92) 564 cases. GD: P = 7.4 × 10-5, OR = 1.79 (95% CI = 1.34–2.39) 351 cases. HT: P = 0.022, OR = 1.62 (95% CI = 1.07–2.47) 158 cases [43]. |
CFH 1q32 (3075) | Complement factor H, a key regulator of the complement system of innate immunity, binds heparin and CRP | His402Tyr (rs1061170) | 0.41 controls, white, not of Hispanic origin | Age-related macular degeneration: (nominal P = <10-7) 96 cases and 50 controls [44]. |
PAD14 1q36.13 (23569) | Peptidylarginine deiminases role in granulocyte & macrophage development, leading to inflammation and immune response, associated with RA. | PADI4-94 (rs2240340) | 0.37 Japanese controls | RA: P = 8 × 10-6, OR = 1.97 (95% CI = 1.44–2.69) 830 cases and 736 controls [45]. |
IL1RN & IL1A 2q14 (3557 & 3552) | Cytokines involved in the inflammatory response, polymorphisms confer susceptibility to RA and Ankylosing spondylitis. | IL1RN+2017 (rs2419598) IL1A-889 (rs1800587) | 0.22 & 0.27, respectively, Caucasian controls | RA: P = 0.008; 406 Dutch cases and 245 controls [46]. Ankylosing spondylitis: P = 0.025; 227 British families, 317 parent-case trios and 200 controls [47]. |
NFKB1 4q24 (4790) | NFκB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NFκB has been associated with a number of inflammatory diseases | (CA) dinucleotide repeat microsatellite | Allele 8, A10 & A14, 0.19, 0.02 and 0.28 respectively, UK controls | T1D: A10: P = 0.000001, OR = 9.4; 434 cases, 222 controls [36]. T1D: no association; 236 Danish families [37]. |
SLC22A4 5q31 (6583) | The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Polymorphisms confer susceptibility to RA. | SLC22A4:F1 (rs2073838) SLC22A4:F2 (rs3792876) | 0.31 & 0.32 respectively, Japanese controls | RA: P = 0.000034, OR = 1.98 (95% CI = 1.43–2.75) 830 cases and 658 controls [48]. CD: P = 0.001, OR = 2.1 (95% CI = 1.31–3.39) 203 cases and 200 controls [49]. |
IBD5 locus 5q31 (50941) | Confers susceptibility to Crohn disease. | IGR2198 (rs11739135) | 0.36 Canadian parental. | CD: P = 0.000048; 256 trios [50]. |
SPINK5 5q32 (11005) | Encodes a 15 domain serine proteinase inhibitor (LEKTI) involved in anti-inflammatory and/or antimicrobial protection of mucous epithelial, polymorphisms associated with atopy, Netherton disease. | 316G>A (ss28514851) 1103A>G (rs2303064) 1156G>A (rs2303063) 1258G>A (rs2303067) 2475G>T (rs2303070) 2915A>G (ss28514856) | 0.03, 0.50, 0.13, 0.48, 0.08 & 0.04, respectively, UK controls | Atopy, Netherton disease: (rs2303064): P = 0.008, (rs2303067): P = 0.002; 148 families [51]. Asthma (rs2303067): P = 0.04, OR = 1.77 (95% CI = 1.02–3.06) 1161 children. Asthma and atopy: P = 0.007, OR = 4.56 (95% CI = 1.37–15.12) 37 German cases and 415 controls [52]. |
FCER1B 11q13 (2206) | Encodes the beta subunit of the high affinity IgE receptor, a member of the membrane-spanning 4A gene family, and displays unique expression patterns among hematopoietic cells and nonlymphoid tissues. Responsible for initiating the allergic response, associated with atopy and atopic asthma. | Gly237Glu (rs569108) | 0.06 Japanese controls | Atopy: two-point lod score 9.35 [17]. Childhood asthma (rs569108): P = <0.002, OR = 3; 200 Japanese cases and 100 controls [16]. |
LAG3 12p13.32 (3902) | Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. | Thr455Ile (rs870849) | N/A | MS: P = 0.005; 576 cases and 662 controls [53]. |
CARD15 16q12 (64127) | Intracellular sensors of bacterial peptidoglycan These SNPs encode amino acid changes located in or near the leucine-rich repeat region, which is involved in peptidoglycan binding, conferring an increased risk of Crohn disease, PA and Blau syndrome. | SNP8 (rs2066844) SNP12 (rs2066845) SNP13 (ss28514842) | 0.04, 0.01 & 0.02, respectively, Caucasian controls | CD (SNP13): P = 6 × 10-6; 235 families [54]. P = 0.0046; 416 families[55]. PA: P = 0.0027, OR = 3.5 (95% CI = 1.51–7.01) [56]. Blau Syndrome [57]. |
SLC9A3R1 17q25 (9368) | Immune synapse formation in T cells, polymorphism associated with psoriasis. | SLC9A3R1 (rs734232) | 0.42 European controls | Psoriasis: P = 0.0009; 134 trios [58]. |
ADAM33 20p13 (80332) | Encodes a disintegrin and metalloprotease (ADAM) domain 33, which is a member of the ADAM protein family. Has a role in cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Reported as an asthma and bronchial hyper-responsiveness susceptibility locus. | ST+4 (rs44707) V4 (rs2787094) Q-1 (rs612709) ST+7 (rs574174) T+1 (rs2280089) T2 (rs2280090) | 0.48, 0.25, 0.24, 0.22, 0.08, 0.07 UK & USA controls | Asthma and bronchial hyperresponsiveness: P = 0.03 – 0.02; 130 cases and 217 controls [35]. P = 0.04–0.0009 in ethnically diverse populations [59]. |
RUNX1 21q22.3 (861) | The RUNX1 transcription factor is expressed mainly in hematopoietic cells and functions both to activate and to repress transcription through interactions with cofactors. This SNP alters a binding site for RUNX1 and has been associated with RA. | RUNX1 (rs2268277) | 0.37 Japanese controls | RA: P = 0.0013, OR= 1.28 (95% CI = 1.10–1.48) 719 cases and 441 controls [48]. |