title: IL6-174G > C genetic polymorphism influences antidepressant treatment outcome.
abstract: BACKGROUND
  Major depressive disorder is a condition associated with dysregulated cytokine levels; among these, IL6. Furthermore, genetic variations within cytokine genes have been proposed to predict antidepressant treatment outcome.
  
  
  OBJECTIVE
  This study aims to evaluate the role of IL6-174G > C and IL6R D358A A > C functional polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse, and treatment resistant depression (TRD).
  
  
  METHODS
  The referred polymorphisms were genotyped in 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months.
  
  
  RESULTS
  It was found that patients carrying IL6-174 GC genotype present a protection towards the development of TRD (OR = 0.242; 95% CI = 0.068-0.869; p = .038), when compared with GG genotype. Additionally, carriers of IL6-174 CC genotype remit earlier than patients with IL6-174 GG/GC genotypes, with a median time to remission of 6 weeks for CC carriers and 15 weeks for GG or GC carriers (p = .030, Log-rank test). No association was found between IL6R D358A genetic polymorphism and any of the treatment phenotypes evaluated.
  
  
  CONCLUSIONS
  The IL6-174G > C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.
authors: a Hospital de Magalhães Lemos , Porto , Portugal.|b Instituto Superior de Ciências da Saúde , Norte , Portugal.
authors: Serafim
authors: S
authors: Carvalho
authors: c Molecular Oncology & Viral Pathology , IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology , Porto , Portugal.|d Núcleo de Investigação e Informação em Farmácia-Centrode Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies , Polytechnic Institute of Porto , Porto , Portugal.|e Faculty of Medicine , University of Porto , Porto , Portugal.
authors: Marlene
authors: M
authors: Santos
authors: f Experimental Pathology and Therapeutics Group , Portuguese Institute of Oncology , Porto , Portugal.
authors: Luís
authors: L
authors: Lima
authors: g Clínica Médico-Psiquiátrica da Ordem , Porto , Portugal.
authors: Jorge
authors: J
authors: Mota-Pereira
authors: h Trás-os-Montes e Alto Douro Hospital Center , Vila Real , Portugal.
authors: Paulo
authors: P
authors: Pimentel
authors: h Trás-os-Montes e Alto Douro Hospital Center , Vila Real , Portugal.
authors: Dulce
authors: D
authors: Maia
authors: a Hospital de Magalhães Lemos , Porto , Portugal.
authors: Diana
authors: D
authors: Correia
authors: a Hospital de Magalhães Lemos , Porto , Portugal.
authors: Sofia
authors: S
authors: Gomes
authors: d Núcleo de Investigação e Informação em Farmácia-Centrode Investigação em Saúde e Ambiente (CISA), School of Allied Health Technologies , Polytechnic Institute of Porto , Porto , Portugal.
authors: Agostinho
authors: A
authors: Cruz
authors: c Molecular Oncology & Viral Pathology , IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology , Porto , Portugal.|i Department of Pathology and Molecular Immunology, ICBAS , Abel Salazar Biomedical Sciences Institute, University of Porto , Porto , Portugal.|j Health Faculty of University Fernando Pessoa, CEBIMED , Porto , Portugal.|k Research Department , Portuguese League Against Cancer (Norte) , Porto , Portugal.
authors: Rui
authors: R
authors: Medeiros
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D011110:Polymorphism, Genetic; D019947:Receptors, Interleukin-6 / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: IL6; antidepressants; genetic polymorphisms; treatment resistant depression