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Influence of Promoter Polymorphisms of the TNF-? (-308G/A) and IL-6 (-174G/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis.

ABSTRACT: The study was undertaken to assess the influence of functional -308G/A TNF-? (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-? blocker, in patients with rheumatoid arthritis (RA).Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G/A TNF-? and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed.No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-?-308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/TNF-? genotypes showed that patients with the IL-6 -174GG / TNF-?-308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chi-square test). More precisely, all patients with the combined IL-6 -174GG / TNF-?-308GG genotype were responders after 12 months of etanercept treatment.The study suggests that patients who are genetically low TNF-? and IL-6 producers are the best responders to etanercept therapy.


PROVIDER: S-EPMC4922353 | BioStudies | 2015-01-01T00:00:00Z


REPOSITORIES: biostudies

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