title: -174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers.
abstract: BACKGROUND
  Although TNF-α blockade is a very effective therapy for psoriasis, not all patients achieve a favorable outcome. The association between IL-6 and psoriasis has been investigated but no papers have focused on the pharmacogenetics of IL-6.
  
  
  OBJECTIVE
  To examine whether the G or the C allele, at position -174 in the promoter of IL-6, influences the relationships between body weight, body composition, and therapeutic response to TNF-α blockers in psoriasis.
  
  
  METHODS
  Sixty patients with psoriasis were studied, at baseline and 6-month follow-up after therapy. Assessment of the -174G/C IL-6 polymorphism, Psoriasis Area and Severity Index and Disease Activity Score-28 scores, body weight (kg), BMI, body composition by Dual-energy X-ray absorptiometry, and systemic inflammation was performed.
  
  
  RESULTS
  Relevant body composition changes occurred after therapy. Normal weight participants showed a greater increase in fat mass than lean mass, compared with obese participants. According to their genotypes, C(+) carriers showed a greater increase in lean mass and fat mass, at the abdominal region, with respect to C(-) carriers. C(+) carriers outweighed C(-) carriers in the group of treatment responders. A higher number of responders were present among normal weight participants, with respect to obese participants. Obesity and the -174G/C IL-6 polymorphism predicted poor response to TNF-α blockers [odds ratio for C(-) carriers, obese: 2.00 (confidence interval: 1.19-3.38; P≤0.05)].
  
  
  CONCLUSIONS
  Our data show that the G allele of the -174G/C IL-6 polymorphism and obesity can be considered as risk factors for the prognosis and management of psoriasis. This is the first study to suggest the -174G/C IL-6 polymorphism as a novel genetic marker of responsiveness to TNF-α blockers in psoriasis.
authors.affiliation: Department of Neuroscience, Division of Human Nutrition, University of Rome Tor Vergata, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Di Renzo
authors.forename: Alessia
authors.initials: A
authors.lastname: Bianchi
authors.forename: Rosita
authors.initials: R
authors.lastname: Saraceno
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
authors.forename: Caroline
authors.initials: C
authors.lastname: Cornelius
authors.forename: Leonardo
authors.initials: L
authors.lastname: Iacopino
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.forename: Antonino
authors.initials: A
authors.lastname: De Lorenzo
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015992:Body Mass Index; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha