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-174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanercept in rheumatoid arthritis

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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.

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Acknowledgments

This work was supported by Ministry of Education and Science of Republic of Serbia (grant numbers, 175050, 175065, III41004).

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The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221, Belgrade, Serbia

    Ivan Jančić & Nevena Arsenović-Ranin

  2. Institute of Rheumatology, Faculty of Medicine, University of Belgrade, 69 Resavska, 11000, Belgrade, Serbia

    Mirjana Šefik-Bukilica, Sladjana Živojinović & Nemanja Damjanov

  3. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 444a Vojvode Stepe, 11221, Belgrade, Serbia

    Vesna Spasovski, Sanja Srzentić, Biljana Stanković & Sonja Pavlović

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  1. Ivan Jančić
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  2. Nevena Arsenović-Ranin
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Correspondence to Nevena Arsenović-Ranin.

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Jančić, I., Arsenović-Ranin, N., Šefik-Bukilica, M. et al. -174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanercept in rheumatoid arthritis. Rheumatol Int 33, 1481–1486 (2013). https://doi.org/10.1007/s00296-012-2586-y

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  • DOI: https://doi.org/10.1007/s00296-012-2586-y

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