title: Confirmation of -174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome.
abstract: BACKGROUND
  The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
  
  
  METHODS
  Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
  
  
  RESULTS
  The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months).
  
  
  CONCLUSIONS
  Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
authors.affiliation: aInstituto de Parasitología y Biomedicina López-Neyra, CSIC bDepartment of Clinical Pharmacy, UGC Farmacia Granada cDepartment of Rheumatology, Instituto de Investigación Biosanitaria de Granada, San Cecilio University Hospital, Granada Departments of dImmunology eRheumatology, IdiPAZ, RIER, La Paz University Hospital, Madrid fDepartment of Rheumatology, Virgen de la Arrixaca University Hospital, Murcia gDepartment of Rheumatology, Virgen de la Victoria University Hospital, Málaga hDepartment of Rheumatology, Doctor Peset Hospital, Valencia, Spain.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Dávila-Fajardo
authors.forename: Ana
authors.initials: A
authors.lastname: Márquez
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Moreno Ramos
authors.forename: Rosa
authors.initials: R
authors.lastname: García-Portales
authors.forename: César
authors.initials: C
authors.lastname: Magro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Alegre-Sancho
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: José
authors.initials: J
authors.lastname: Cabeza-Barrera
authors.forename: Enrique
authors.initials: E
authors.lastname: Raya
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D003596:Cytosine; D000068800:Etanercept; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006147:Guanine; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D000069285:Infliximab; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D005819:Genetic Markers; C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D003596:Cytosine; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept