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Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-α-308GG genotype

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Abstract

Genetic contribution of tumor necrosis factor polymorphism (TNF-α-308G/A) in patients with juvenile idiopathic arthritis (JIA) on response to TNF blocking agents, as well as matrix metalloproteinase-9 (MMP-9) production, is not yet well established. We have investigated whether the TNF-α-308G/A polymorphism can influence MMP-9 level and clinical response to etanercept (TNF receptor II-Fc fusion protein) in JIA patients, after 1 year of treatment. A total of 66 patients with polyarticular JIA and 65 healthy children were screened for the polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. JIA patients donated paired blood samples prior to and 12 months after etanercept therapy. Plasma MMP-9 level was determined using an enzyme-linked immunosorbent assay kit. Clinical assessment was performed according to ACR Pedi 50 improvement criteria. The frequency of the A allele was significantly higher in JIA patients compared to controls (39% vs. 26%, P = 0.026). Patients with the −308GG genotype achieved an ACR Pedi 50 response significantly more frequently than those with the −308AA genotype (P = 0.035). MMP-9 level in patients with the genotype −308GG was significantly decreased after 1 year of treatment with etanercept compared to the value from before (P = 0.036). On the other hand, there was a decrease of MMP-9 levels after treatment, but not statistically significant in patients with the genotypes −308GA/AA. We conclude that etanercept reduces MMP-9 level in children with polyarticular JIA and TNF-α-308GG genotype. Our results correlate with findings that the −308A allele is associated with a lower response to etanercept treatment.

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Acknowledgment

This study was supported by the Ministry of Science of the Republic of Serbia (grant no. 145081).

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Authors and Affiliations

  1. Institute of Biochemistry, Medical Faculty, University of Nis, Bulevar dr Zorana Djindjica 81, 18000, Nis, Serbia

    Jelena Basic, Dusica Pavlovic, Tatjana Jevtovic-Stoimenov, Ivana Stojanovic, Gordana Kocic, Tatjana Cvetkovic, Milena Marinkovic & Andrej Veljkovic

  2. Clinic of Pediatrics, Clinical Centre Nis, Nis, Serbia

    Jelena Vojinovic

  3. Institute of Rheumatology, Belgrade, Serbia

    Gordana Susic

  4. Clinic of Neurology, Clinical Centre Nis, Nis, Serbia

    Vuk Milosevic

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  1. Jelena Basic
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  2. Dusica Pavlovic
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Correspondence to Jelena Basic.

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Basic, J., Pavlovic, D., Jevtovic-Stoimenov, T. et al. Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-α-308GG genotype. J Physiol Biochem 66, 173–180 (2010). https://doi.org/10.1007/s13105-010-0022-x

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  • DOI: https://doi.org/10.1007/s13105-010-0022-x

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