I review two examples of such challenges: the cloning of GPR154 (GPRA) and AAA1 on chromosome 7p14 at a susceptibility locus for atopy and asthma, and the study of HLA-Cw6, CCHCR1 (HCR) and CDSN on chromosome 6p21 at PSORS1, the major susceptibility locus for psoriasis.
To identify the mutations responsible for the psoriasis in this family, we sequenced 78 genes within the region and found four gene variants, p.Ala201Val in CD7, c.-625A>C in zinc-finger protein 750 (ZNF750), p.Asp189Asn in C17orf56, and p.Ala568Thr in AATK cosegregated with the disease.
SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity.
SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity.
As ACC haplotype is suggested to be associated with high IL-10 secretion and ATA is related to low IL-10 secretion, potential differences in the IL-10 secretion levels might contribute the differences in the clinical course of psoriasis.
Genome-wide association studies (GWAS) in several populations have demonstrated significant association of the IL23R gene with IBD (Crohn's disease (CD) and ulcerative colitis (UC)) and psoriasis, suggesting that perturbation of the IL-23 signaling pathway is relevant to the pathophysiology of these diseases.
More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.
DISCUSSION: Because the concurrent existence of psoriatic arthritis and IBD is becoming increasingly appreciated in recent literature, healthcare providers should have a high index of suspicion in patients with psoriasis and psoriatic arthritis presenting with unusual intestinal symptoms.
The overall prevalence rate of IBD and psoriasis was 2.4% ( n = 33), with 1.8% ( n = 25) in the Crohn's disease group and 0.6% ( n = 8) in the ulcerative colitis group.
Clinical characteristics were comparable between IBD patients with or without psoriasis: age 50 [23-72] vs 47 [16-85]; IBD duration 9.5 [1-46] vs 9 [1-41]; p = non-significant].
The RR (95% CI) in individuals with a first-degree relative with RA was 2.91 (2.49, 3.42) for SLE; 2.92 (1.62, 5.25) for SSc; 3.13 (2.50, 3.93) for primary SS; 0.95 (0.36, 2.51) for idiopathic inflammatory myositis; 1.96 (1.54, 2.48) for type 1 diabetes mellitus; 3.32 (1.82, 5.95) for multiple sclerosis; 1.31 (1.31, 2.43) for IBD; 2.76 (2.46, 3.10) for AS; and 1.65 (1.54, 1.77) for psoriasis.
In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10(-5), OR 1.3), when cases with IBD and/or psoriasis were excluded.
Although there are many similarities among AS patients possessing HLA-B*27 versus those lacking this gene, the former group has a younger age of onset, a shorter delay in diagnosis, a better clinical response to tumor necrosis factor inhibitors, a greater familial occurrence, a greater risk for occurrence of acute anterior uveitis, and a lower risk for occurrence of psoriasis and IBD.
This review will focus on the interplay between IBD and PS, with details on prevalence and phenotype of PS in IBD, genetics, pathogenetic pathways, and therapy.