title: Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis.
abstract: BACKGROUND
  The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response.
  
  
  OBJECTIVE
  We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort.
  
  
  METHODS
  We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2-test or Fisher's exact test (PASI 75, secondary analysis).
  
  
  RESULTS
  We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis.
  
  
  CONCLUSIONS
  We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: J M P A
authors: JMPA
authors: van den Reek
authors: Department of Human Genetics, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: M J H
authors: MJH
authors: Coenen
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: M
authors: M
authors: van de L'Isle Arias
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: J
authors: J
authors: Zweegers
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: D
authors: D
authors: Rodijk-Olthuis
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: J
authors: J
authors: Schalkwijk
authors: Department of Health Evidence, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: S H
authors: SH
authors: Vermeulen
authors: Department of Immunology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: I
authors: I
authors: Joosten
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: P C M
authors: PCM
authors: van de Kerkhof
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: M M B
authors: MMB
authors: Seyger
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: P L J M
authors: PLJM
authors: Zeeuwen
authors: Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
authors: E M G J
authors: EMGJ
authors: de Jong
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D005819:Genetic Markers; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000235:genetics; D016896:Treatment Outcome; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics; D000069549:Ustekinumab / Q000627:therapeutic use
chemical_list: D001688:Biological Products; C498970:CD84 protein, human; D003879:Dermatologic Agents; D005819:Genetic Markers; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D000071176:Signaling Lymphocytic Activation Molecule Family; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000069549:Ustekinumab; D000068879:Adalimumab; D000068800:Etanercept