title: Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-alpha-308GG genotype.
abstract: Genetic contribution of tumor necrosis factor polymorphism (TNF-alpha-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-alpha-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-alpha-308GG genotype. Our results correlate with findings that the -308A allele is associated with a lower response to etanercept treatment.
authors.affiliation: Institute of Biochemistry, Medical Faculty, University of Nis, Bulevar dr Zorana Djindjica 81, 18000 Nis, Serbia. jelenabasic@yahoo.com
authors.forename: Jelena
authors.initials: J
authors.lastname: Basic
authors.forename: Dusica
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Jelena
authors.initials: J
authors.lastname: Vojinovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Susic
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojanovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocic
authors.forename: Vuk
authors.initials: V
authors.lastname: Milosevic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Cvetkovic
authors.forename: Milena
authors.initials: M
authors.lastname: Marinkovic
authors.forename: Andrej
authors.initials: A
authors.lastname: Veljkovic
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002648:Child; D000068800:Etanercept; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D000068800:Etanercept