Alessandra Scardapane1, Rossella Ferrante2, Manuela Nozzi1, Alessandra Savino1, Ivana Antonucci2, Vincenzo Dadorante1, Michela Balsamo3, Liborio Stuppia2, Francesco Chiarelli1, Luciana Breda4. 1. Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy. 2. Laboratory of Molecular Genetics, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy. 3. Psycometric Laboratory, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy. 4. Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy. Electronic address: luciana.breda@tin.it.
Abstract
OBJECTIVE: To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with juvenile idiopathic arthritis (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 positions -163, -244, -238, -376, and -308. RESULTS: No SNPs at position -163 were observed, while we observed only SNPs at positions -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 and p = 0.013, respectively) and 12 months of disease (p = 0.02 and p = 0.08, respectively). Also the -238 GG genotypes showed a better disease course after 12 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 12 months 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 -308 AA 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.
OBJECTIVE: To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with juvenile idiopathic arthritis (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 positions -163, -244, -238, -376, and -308. RESULTS: No SNPs at position -163 were observed, while we observed only SNPs at positions -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 and p = 0.013, respectively) and 12 months of disease (p = 0.02 and p = 0.08, respectively). Also the -238 GG genotypes showed a better disease course after 12 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 12 months 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 -308 AA 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.
Authors: Faekah Gohar; Janneke Anink; Halima Moncrieffe; Lisette W A Van Suijlekom-Smit; Femke H M Prince; Marion A J van Rossum; Koert M Dolman; Esther P A H Hoppenreijs; Rebecca Ten Cate; Simona Ursu; Lucy R Wedderburn; Gerd Horneff; Michael Frosch; Dirk Foell; Dirk Holzinger Journal: J Rheumatol Date: 2018-01-15 Impact factor: 4.666