title: -174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanercept in rheumatoid arthritis.
abstract: To examine whether -174G/C interleukin-6 (IL-6) gene polymorphism, previously reported to correlate with IL-6 level, influences response to etanercept therapy in patients with rheumatoid arthritis. Seventy-seven patients with active RA were studied, at baseline and 6- and 12-month follow-up after etanercept therapy. Treatment response was estimated according to the European League Against Rheumatism response criteria. RA patients were genotyped for -174G/C IL-6 gene polymorphism by the PCR-RFLP method, and influence of genotype at this polymorphism to clinical response to etanercept was assessed. After 12 months of treatment, the percentage of responders (patients who had DAS28 improvement >1.2) was significantly increased in patients carrying the IL-6 -174G/G genotype (95.7 %) compared with those with the G/C (75.6 %) or CC (44.4 %) genotype (p = 0.006 by Chi-square test). No significant difference in the mean values of DAS28 improvement was observed between groups with different genotype. RA patients with an IL-6 -174GG genotype respond to etanercept better than patients with GC or CC genotype. This finding, if confirmed in future studies, suggests that the -174G/C IL-6 polymorphism may be a genetic marker of responsiveness to tumor necrosis factor-alpha (TNF-α) blockers in RA.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Jančić
authors.forename: Nevena
authors.initials: N
authors.lastname: Arsenović-Ranin
authors.forename: Mirjana
authors.initials: M
authors.lastname: Sefik-Bukilica
authors.forename: Sladjana
authors.initials: S
authors.lastname: Zivojinović
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.forename: Vesna
authors.initials: V
authors.lastname: Spasovski
authors.forename: Sanja
authors.initials: S
authors.lastname: Srzentić
authors.forename: Biljana
authors.initials: B
authors.lastname: Stanković
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlović
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D000068800:Etanercept; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept