Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The exact cause of the disease is still unknown, but seems to be related to both genetic and environmental factors . The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene single-nucleotide polymorphism (SNP) rs2476601 was shown to be associated with JIA in different populations, but according to resent reports this association is restricted only to females [2,3].
Objectives The aim of the study was to determine whether the PTPN22 rs2476601 SNP is associated with the development of JIA and its subtypes in children from Russia.
Methods The study included 330 patients with JIA and 346 healthy controls from Russia. Genotyping was performed using real-time PCR method and statistical analysis - using two-tailed Fisher's exact test (p), odds ratio (OR), 95% confidence interval (95% CI).
Results The frequencies of the genotype AG and the allele A were significantly higher and the frequencies of the genotype GG and the allele G were significantly lower in patients with JIA than in controls (p=0.016, OR=1.65, 95% CI 1.10–2.48; p=0.028, OR=1.48, 95% CI 1.05–2.08; p=0.016, OR=0.62, 95% CI 0.43–0.91; p=0.028, OR=0.68, 95% CI 0.48–0.95, correspondingly). The same analysis was then performed separately for patients with two the most frequent ILAR subtypes: persistent oligoarthritis (n=106) and RF-negative polyarthritis (n=85). Significant associations similar to those in the whole JIA group were found only for persistent oligoarthritis (p=0.018 for the genotype AG; p=0.037 for the allele A; p=0.022 for the genotype GG; p=0.037 for the allele G). No significant differences were found for patients with RF-negative polyarthritis (p>0.6). Sex-stratified analysis showed that for the whole JIA group and for persistent oligoarthritis the association with the PTPN22 rs2476601 SNP is restricted only for girls (for girls with the genotype AG: p=0.024 and p=0.0098; with the allele A: p=0.016 and p=0.0061; with the genotype GG: p=0.015 and p=0.0047; with the allele G: p=0.016 and p=0.0061, correspondingly; for boys: p>0.2 for all comparisons).
Conclusions In this study we revealed the association of the PTPN22 rs2476601 SNP with the development of JIA and its persistent oligoarticular subtype in girls from Russia.
Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369:767–778.
Chiaroni-Clarke RC, Li YR, Munro JE, Chavez RA, Scurrah KJ, Pezic A, et al. The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes Immun. 2015;16:495–498.
Goulielmos GN, Chiaroni-Clarke RC, Dimopoulou DG, Zervou MI, Trachana M, Pratsidou-Gertsi P, Garyfallos A, Ellis JA. Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population. Pediatr Rheumatol Online J. 2016 Apr 23;14(1):25.
Disclosure of Interest None declared