title: Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis.
abstract: BACKGROUND
  The CARD14 gene encodes a protein that enhances nuclear factor (NF)-κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis.
  
  
  OBJECTIVE
  To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis.
  
  
  METHODS
  DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments.
  
  
  RESULTS
  A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04).
  
  
  CONCLUSIONS
  The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.
authors: Department of Dermatology, Hospital Universitario Central Asturias, Oviedo, Spain.|Deparment of Medicine, Universidad Oviedo, Oviedo, Spain.
authors: P
authors: P
authors: Coto-Segura
authors: Department of Dermatology, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: D
authors: D
authors: González-Fernández
authors: Department of Dermatology, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: A
authors: A
authors: Batalla
authors: Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: J
authors: J
authors: Gómez
authors: Department of Dermatology, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: L
authors: L
authors: González-Lara
authors: Department of Reumatology, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: R
authors: R
authors: Queiro
authors: Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: B
authors: B
authors: Alonso
authors: Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: S
authors: S
authors: Iglesias
authors: Deparment of Medicine, Universidad Oviedo, Oviedo, Spain.|Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain.
authors: E
authors: E
authors: Coto
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D053468:CARD Signaling Adaptor Proteins; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; C426243:CARD14 protein, human; D006162:Guanylate Cyclase; D000068879:Adalimumab; D000068800:Etanercept