Table 1.
Genetic susceptibility loci associated with psoriasis and IBD
| Locus | Candidate implicated genes | Protein | Function | Psoriasis association with relevant SNP | IBD association with relevant SNP | Comment |
|---|---|---|---|---|---|---|
| 6p21 | CDKAL1 | Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 | Unknown (shared domain with CDK5 protein inhibitor) | Low levels of protein expression in lesions SNPs (rs6908425) appear as risk factors.180 |
Low levels of protein expression in lesions SNPs (rs11584383) appear as risk factors.181 |
Similar pathophysiology; divergent SNPs |
| 1p31.1 | IL-23R | Interleukin-23 receptor | Inflammatory mediator | Protective (rs7530511) and predisposing (rs11209026) SNP polymorphisms.182 | Protective (rs11209026, rs7517847) and predisposing SNP polymorphisms (rs11805303) for Crohn’s disease.17,183 | Existence of risk modifying polymorphisms for psoriasis and Crohn’s disease; however, different SNPs and even risk directions for the same SNP (eg, rs11209026). |
| 16q | NOD2/CARD15 | Nucleotide-binding oligomerization domain-containing protein 2 (also known as caspase recruitment domain-containing protein 15) | Intracellular protein in the proinflammatory NFκB pathway | NOD2/CARD15 polymorphisms are not connected to psoriasis. However, a psoriasis susceptibility locus on chromosome 16q near marker D16S3110 is identified.17 | At least three NOD2/CARD15 gene variants (3020insC, R702W, G908R) have been identified as genetic risk factors for Crohn’s disease patients.17 | No evidence for pathophysiologic connection at gene level. Divergent susceptibility genes within the same locus. |
| 5q33.1 | IL12B | Interleukin-12 subunit β | Encodes the common IL-12 p40 subunit of IL-12 and IL-23 | Strong association with PSORS 11 psoriasis susceptibility locus. Various SNPs (rs7709212, rs10045431, rs3212227, rs6887695) have been identified.184 | Strong association with IBD19, IBD susceptibility locus. Various SNP recognized as risk factors (rs6887695, rs13361189, rs4958847).185 | Established susceptibility loci for both diseases; however, divergent polymorphisms. |
| 20q13s | Psoriasis: RNF114 IBD: TNFRSF6B |
Ring finger protein 114 Tumor necrosis factor receptor superfamily member 6B |
RNF11 participates in Type I IFN production. TNFRSF6B acts as a decoy receptor (DCR3) in preventing FasL-induced cell death. |
A single cluster of disease-associated markers, spanning 47 kb on chromosome 20q13. Multiple SNPs (as rs495337) were identified with a putative role in the regulation of immune responses.186 |
A locus at chromosome 20q13 has been associated with IBD. rs2315008T and rs4809330A were present in the tested IBD population with an odds ratio of 0.74.187 | No evidence for pathophysiologic connection at gene level. Divergent susceptibility genes within the same locus. |
| 19p13 | Psoriasis: BSG JunB MUC16 IBD: ICAM1 C3 TBXA2 LTB4H TYK2 and JAK3 |
Basigin JunB Mucin 16 Intercellular adhesion molecule 1 Complement component 3 Thromboxane A2 receptor Leukotriene B4 hydroxylase Janus protein tyrosine kinases TYK2 and JAK3 |
Basigin possess a fundamental role in intercellular recognition JunB is a transcription factor Glycoprotein, known biomarker Critical molecules in inflammatory pathways, immune responses, and cell activation |
A susceptibility factor at chromosome 19p13 had been identified and associated with SNP rs12459358.188 | A locus on 19p13 confers susceptibility to both Crohn’s disease and ulcerative colitis.189 This is located around microsatellite marker D198247. | No evidence for pathophysiologic connection at gene level. Divergent susceptibility genes within the same locus. |
| 6p21 | HLA-Cw6 | HLA-CW6 | HLA-C belongs to the MHC Class I heavy chain receptors | PSORS1 is the strongest susceptibility locus detectable by family-based linkage studies and accounting for one-third to one-half of the genetic liability to psoriasis.180 Candidate SNPs include among others rs1050414 and rs697743. |
Crohn’s disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD.190 | Probably not a pathophysiologic connection; a locus of strong genetic linkage between psoriasis and IBD. |
| 5q31 | IL-4, IL-5, IL-13 | Interleukins 4, 5, and 13 | Inflammatory mediators | A SNP in the 3′-untranslated region of the IL12B gene on chromosome 5q31-33 has been associated with psoriasis.182 Two other SNPs offer either protection (rs7709212) or favored disease appearance (rs10045431). | SNP rs6596075 corresponding to a risk haplotype on 5q31 have been associated with Crohn’s disease along with rs2188962 on 5q31.191 | Probably a genetic linkage; divergent SNPs. |
Notes: Genetic association studies have discovered various genome areas that are associated with both diseases. Only eight loci are described with well-established associations for both diseases. However, within the same locus, the involved genes and polymorphisms may diverge between the skin and gut diseases.
Abbreviations: SNP, single nucleotide polymorphism; IBD, inflammatory bowel disease; MHC, major histocompatibility complex.