Background One of the most important molecules involved in juvenile idiopathic arthritis (JIA) is the Tumor Necrosis Factor-α (TNF-α), since several studies have demonstrated increased TNF-α levels in both serum and synovial fluid of children with chronic arthritis. Moreover, the proven efficiency of anti TNF-α biologic drugs in JIA patients suggests a key role for this cytokine.
Several single nucleotide polymorphisms (SNPs) have been identified within the promoter, exonic, intronic, and 3'untranslated region of the TNF-α gene, but conflicting results about the role of these variants in JIA have been reported and only a very small minority of these genetic variants have proven to be correlated with disease phenotype and/or clinical outcome.
Objectives To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with JIA.
Methods 74 Caucasian patients with JIA were recruited with a control group of 77 healthy children. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position -163, -244, -238, -376 and -308.
Results No SNPs at position -163 were observed while we observed only SNPs at position -244 and -376 in the controls. No differences were observed in the prevalence of SNPs at -238 and -308 between JIA and controls. In JIA patients no significant differences were observed between the -238 and -308 G/A genotypes and different disease phenotypes. We observed a significant lower disease activity expressed in the carriers of -308 GG genotype with respect to GA and AA genotypes after 6 (p=0.008 p=0.013 respectively) and 12 months of disease (p=0.02 p=0.08 respectively). Also the -238 GG genotypes showed a better disease course after12 months of disease. Moreover the -238/-308 GG genotypes presented the higher reduction of disease activity both after 6 (p<0.01 vs GA and p<0.01 vs AA) and 12months from baseline (p<0.01 vs GA and p<0.01 vs AA). After 12 months of biologic therapy, a significant higher disease activity was observed in patients with genotype -308AA respect to both GA (p=0.012) and GG (p=0.016).
Conclusions JIA patients carrying the TNF-α -308 GA/AA and -238 GA genotypes are associated with a worse prognosis and with a lower response to anti-TNF-α drugs.
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Hajeer AH, Hutchinson IV. TNF-alpha gene polymorphism: clinical and biological implications. Microsc Res Tech 2000;50(3):216-28.
Disclosure of Interest None declared