TNF-α gene polymorphisms and juvenile idiopathic arthritis: Influence on disease outcome and therapeutic response.

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 p p p 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.