Genetic basis of TNF‐α antagonist associated psoriasis in inflammatory bowel diseases: a genotype‐phenotype analysis

Summary Background Anti‐tumour necrosis factor (anti‐ TNF ) biologic associated psoriasis has been reported in inflammatory bowel disease ( IBD ) patients. However, little is known regarding its pathogenesis. Aim To identify potential genetic predispositions to anti‐ TNF associated psoriasis in IBD patients. Methods This retrospective chart review included IBD patients enrolled in a prospective registry. Cases of anti‐ TNF associated psoriasis and idiopathic psoriasis unrelated to anti‐ TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre‐disposition towards psoriasis was calculated and overall genetic pre‐disposition as well as differential distribution of individual polymorphisms was compared across the three groups. Results Our study included 724 IBD patients who initiated anti‐ TNF therapy and did not develop psoriasis, 35 patients with anti‐ TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti‐ TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti‐ TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS 2 and ETS 1 genes achieved P < 0.05 when comparing anti‐ TNF associated psoriasis to anti‐ TNF controls. Three loci were significantly different between anti‐ TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS 2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. Conclusion Patients with anti‐ TNF associated psoriasis had a modestly greater genetic pre‐disposition towards psoriasis but no single causative polymorphism was identified.