Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis

Abstract

Objective. Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 singlenucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes.Methods. Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n ‫؍‬ 472) and population controls (n ‫؍‬ 594), using 5 allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n ‫؍‬ 218) and patients with early undifferentiated inflammatory arthritis (n ‫؍‬ 386). Allele and estimated haplotype frequencies were compared between patients and controls.Results. No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P ‫؍‬ 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P ‫؍‬ 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis.

Severe Skin Lesions Cause Patients With Inflammatory Bowel Disease to Discontinue Anti–Tumor Necrosis Factor Therapy

“…Common susceptibility genes have been identified in CD and psoriasis. 21 Ten patients (43%) with eczematiform lesions and 28 patients (45%) with psoriasiform lesions were smokers. Palmoplantar lesions, which can be triggered by smoking, 22 were observed in 22 patients of whom 15 (68%) were smokers.…”

Psoriasis: Epidemiology, Clinical and Histological Features, Triggering Factors, Assessment of Severity and Psychosocial Aspects

“…It is controversial whether or not the skin condition and arthritis represent a different manifestation of the same disease. Immunological studies, genetic evidence and different responses to treatment, suggest that they might be different conditions with a similar underlying inflammatory process (Pitzalis, Cauli et al 1996;Ho, Bruce et al 2005).…”

Meta-analysis of NOD2/CARD15 polymorphisms with psoriasis and psoriatic arthritis

“…Since Lee FI et al [9] described a potential association between psoriasis and Crohn's disease, possible association of the NOD2/CARD15 polymorphisms R702W, G908R, and Leu1007fsinsC with psoriasis and PsA have been studied among Italian, UK, German, Canada, US, and Spain patients [15][16][17][18][19][20][21][22][23]. However, results are controversial.…”