Table 1.
Chromosomal loci of susceptibility for IBD
| Genetic marker | Locus | Candidate gene(s) | Proposed role(s) in inflammation | Related disease | Associated polymorphism(s) | Reference(s) | PMID |
| IBD1 | 16q12 | NOD2/CARD15, CD19, sialophorin, CD11 integrin cluster, IL4R | Detection of cytosolic bacterial components | CD; UC? | SNPs D16S409 and D16S419 | Hugot, et al. 1996 | 11385576 |
| SNPs D16S409 and D16S753 | Cavanaugh, et al. 1998 | 9924607 | |||||
| SNP D16S3117 | Zouali, et al. 2001 | 11781683 | |||||
| IBD2 | 12p13.2-q24.1 | STAT6, VDR, IFNγ | Development of T-cell response | CD + UC | SNP D12S83 | Duerr, et al. 1998 | 9634527 |
| IBD3 | 6p21.3 | MHC HLA-DQA1, HLA-DRA, HLA-DRB5 and HLA-DRB1, TNFalpha, TNFbeta, IL10, BTLN2 | Detection of non-self components | CD + UC | SNPs D6S289 and D6S276 | Hampe, et al. 1999 | 10053016 |
| IBD4 | 14q11-q12 | MMP14, DAD1, TCR | Development of T-cell response | CD | SNP D14S261 | Duerr, et al. 2000 | 10747815 |
| IBD5 | 5q31 | IL3, IL4, IL5 and IL13, OCTN1, OCTN2, CSF2, SLC22A5 | Regulation of inflammation | CD | SNPs rs6596075 and rs2188962 | Rioux, et al. 2000–2001 | 11586304, 10777714 |
| IBD6 | 19p13 | ICAM-1, C3, TBXA2R, LTB4H | Diapedesis, stimulation of neutrophil response | CD + UC | ns | Van Heel, et al. 2003 | 12928481 |
| IBD7 | 1p36 | PADI4 | ns | CD + UC | SNPs D1S1597, D1S507 and D1S1628 | Cho, et al. 1998–2000 | 9636179, 10814724 |
| IBD8 | 16p | ns | ns | UC | SNP D16S408 | Annese, et al. 2003 | 14627676 |
| IBD9 | 3p26 | DEC1 | Anti-neoplasia | CD + UC | SNP D3S1297 | Duerr, et al. 2002 | 12354785 |
| IBD10 | 2q37.1 | ATG16L1 | Autophagy | CD | SNP rs2241880 | Hampe, et al. 2007 | 17200669 |
| IBD11 | 7q22 | MUC3A | Protection of the epithelial barrier | CD + UC | SNP D7S669 | Satsangi, et al. 1996 | 8841195 |
| IBD12 | 3p21 | MST1, BSN, GNAI2 | Regulation of proinflammatory mediators expression | CD + UC | SNP D3S2432 | Paavola, et al. 2001 | 11378820 |
| IBD13 | 7q21.1 | ABCA1 | Regulation of glucocorticosteroids production? | CD + UC | SNP D7S669 | Satsangi, et al. 1996 | 8841195 |
| IBD14 | 7q32 | IRF5 | Regulation of proinflammatory mediators expression | CD + UC | CGGGG insertion in the promoter of the gene IRF5 | Dideberg, et al. 2007 | 17881657 |
| IBD15 | 10q21 | ZNF365 | Regulation of proinflammatory mediators expression? | CD + UC | SNP rs224136 | Rioux, et al. 2007 | 17435756 |
| SNP rs10761659 | Fisher, et al. 2008 | 18438406 | |||||
| SNP rs10995271 | Barrett, et al. 2008 | 18587394 | |||||
| IBD16 | 9q32 | TNFSF15 | Costimulation of activated T CD4+ cells | CD + UC | SNP D9S2157 | Cho, et al. 1998 | 9636179 |
| SNPs rs3810936, rs6478108, rs6478109, rs7848647 and rs7869487 | Yamakasi, et al. 2005 | 16221758 | |||||
| SNP rs4263839 | Barrett, et al. 2008 | 18587394 | |||||
| IBD17 | 1p31.1 | IL23R, PTGER4 | Generation and maintenance of Th17 cells; prostaglandins signaling | CD + UC | R381Q substitution in IL23R (rs11209026) | Libioulle, et al. 2007 | 17447842 |
| SNP rs7517847 | Rioux, et al. 2007 | 17435756 | |||||
| SNP rs4613763 | Barrett, et al. 2008 | 18587394 | |||||
| IBD18 | 5p13.1 | Gene modulating PTGER4? | Prostaglandins signaling? | CD + UC | SNP rs1373692 | Libioulle, et al. 2007 | 17447842 |
| SNP rs4613763 | Barrett, et al. 2008 | 18587394 | |||||
| SNP rs1992660 | Franke, et al. | 2007 18438405 | |||||
| IBD19 | 5q33.1 | IRGM, IL12B | Autophagy | CD | SNP IL12B rs6887695 | Parkes, et al. 2007 | 17554261 |
| SNP IL12B rs6556416 | Fisher, et al. 2008 | 18438406 | |||||
| SNPs IRGM rs4958847 and rs4958427 | Franke, et al. 2007 | 18438405 | |||||
| SNPs IRGM rs11747270 and rs10045431 | Barrett, et al. 2008 | 18587394 | |||||
| IBD20 | 10q23-q24 | DLG5, NKX2-3 | Maintaining epithelial integrity | CD + UC | SNPs rs11190140 and rs10883365 | Franke, et al. 2008 | 18438405 |
| SNPs D10S547 and D10S20 | Hampe, et al. 1999 | 10053016 | |||||
| SNP rs10883365 | Parkes, et al. 2007 | 17554261 | |||||
| IBD21 | 18p11 | NDUFV2, VAPA, PACAP, PTPN2 | TCR signaling | CD + UC | SNP PTPN2 rs2542151 | Parkes, et al. 2007 | 17554261 |
| IBD22 | 17q21 | STAT3, ORMDL3 | Development of T cell response | CD | SNP ORMDL3 rs2872507 | Barrett, et al. 2008 | 18587394 |
| SNP STAT3 rs744166 | Franke, et al. 2008 | 18438405 | |||||
| IBD23 | 1q32 | IL10 | Regulation of inflammatory mediators production | CD + UC | SNP-1082G | Fowler, et al. 2005 | 15937090 |
| SNP rs17419032 | Franke, et al. 2008 | 18438405 | |||||
| SNP rs3024505 | Franke, et al. 2008 | 18836448 | |||||
| IBD24 | 20q13 | TNFRSF6B or DCR3 | Costimulation of activated T CD4+ cells | CD + UC | SNPs rs2315008 and rs4809330 | Kugathasan, et al. 2008 | 18758464 |
| IBD25 | 21q22 | PSMG1 | Autophagy | CD + UC | SNP rs2836878 | Kugathasan, et al. 2008 | 18758464 |
| IBD26 | 12q15 | ns | ns | UC | SNPs rs1558744, rs7134599, rs2870946 | Silverberg, et al. 2009 | 19122664 |
| IBD27 | 13q13.3 | ns | ns | CD | SNPs rs20411 | Shugart, et al. 2008 | 18246054 |
| UC | SNPs rs17085007 | Asano, et al. 2009 | 19915573 | ||||
| IBD28 | 21q22 | IL10RA | Regulation of inflammation | CD + UC | SNPs rs2836878 | Glocker, et al. 2009 | 19890111 |
ns, not specified; ABC, ABC transporter; ATG16L1, autophagy-related protein 16-1; BSN, Bsn nuclease; C3, complement C3; CD, cluster of differentiation or Crohn disease; CSF, colony stimulating factor; DAD, daughters against ddp protein; DCR, decoy receptor; DEC, differentially expressed in chondrocytes; DLG, disc large homolog; GNAI, guanine nucleotide binding protein, alpha inhibiting; IBD, inflammatory bowel disease; ICAM, intercellular adhesion molecule; IL, interleukin; IFN, interferon; IRF, interferon regulatory factor; IRGM, immunity-related GTPase family, M protein; HLA, human leukocyte antigen; LTB4, leukotriene B4; MHC, major histocompatibility complex; MMP, matrix metalloprotease; NFκB, nuclear factor kappaB; MST, microtubule stabilizing; MUC, mucin; NDUFV, NADH dehydrogenase ubiquinone flavoprotein; NKX, homeodomain protein NKX; NOD2/CARD15, nucleotide-binding oligomerization domain/caspase-activating recruitment domain 15; OCTN, organic cation transporter; ORMDL, orosomucoid (ORM)-like protein family; PACAP, pituitary adenylate cyclase-activating polypeptide; PADI, peptidylarginine deiminase; PSMG, proteasome assembly chaperone; PTGER, G-protein coupled, E-series prostaglandin receptor; PTPN, protein tyrosine-phosphatase; SLC, chemokine CCL21; SNP, single nucleotide polymorphism; STAT, signal transducers and activator of transcription; TBXA2, thromboxane receptor A2; TCR, T-cell receptor; TGF, transforming growth factor; TLR, toll-like receptor; TNF, tumor necrosis factor; TNFSF, tumor necrosis factor superfamily; UC, ulcerative colitis; VAPA, vesicle-associated protein A; VDR, vitamin D receptor; ZNF, zinc finger protein. Reference publication: Wellcome Trust Case Control Consortium: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661–78; PMID: 17554300.