title: The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study.
abstract: BACKGROUND
  Antitumour necrosis factor (anti-TNF)-α agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents.
  
  
  OBJECTIVE
  To study the association of single nucleotide polymorphisms (SNPs) of the TNF-α promoter and IL12B/IL23R genes with the response to anti-TNF-α in patients with psoriasis.
  
  
  METHODS
  SNPs for the TNF-α promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)].
  
  
  RESULTS
  Patients with the TNF-α-238GG genotype more frequently achieved a PASI75 at 6 months (82·5% vs. 58·8%, P = 0·049). At 6 months, patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI score and BSA (83·1% vs. 92·7%, P = 0·004; 82·7% vs. 92·6%, P = 0·009) and more frequently achieved PASI75 (71·4% vs. 96·3%, P = 0·006). More patients with the TNF-α-1031TT genotype achieved PASI75 at 3 months (90·8 vs. 75·7, P = 0·047) and 6 months (85·5% vs. 65·7%, P = 0·038) and demonstrated superior improvements in PASI at 6 months (89·9% vs. 78·7%, P = 0·041). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6 months more frequently (66·3% vs. 0, P = 0·006) and the improvement of the PASI score was also greater (86·8% vs. 67·8%, P = 0·013). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype.
  
  
  CONCLUSIONS
  This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.
authors.affiliation: Department of Dermatology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), C/Diego de León 62, 28006, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.forename: T
authors.initials: T
authors.lastname: Cabaleiro
authors.forename: M
authors.initials: M
authors.lastname: Román
authors.forename: G
authors.initials: G
authors.lastname: Solano-López
authors.forename: F
authors.initials: F
authors.lastname: Abad-Santos
authors.forename: A
authors.initials: A
authors.lastname: García-Díez
authors.forename: E
authors.initials: E
authors.lastname: Daudén
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D016022:Case-Control Studies; D003879:Dermatologic Agents / Q000627:therapeutic use; D000068800:Etanercept; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; C508438:IL12RB1 protein, human; C515500:IL23R protein, human; D007074:Immunoglobulin G; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept