title: Genetic basis of TNF-α antagonist associated psoriasis in inflammatory bowel diseases: a genotype-phenotype analysis.
abstract: 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.
  
  
  OBJECTIVE
  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 NOS2 and ETS1 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 NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis.
  
  
  CONCLUSIONS
  Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Vedak
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kroshinsky
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: St John
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Yajnik
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Ananthakrishnan
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D010641:Phenotype; D011446:Prospective Studies; D011565:Psoriasis / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha