Peculiarities of the Course of Juvenile Arthritis Depending on the Polymorphism of Proinflammatory Cytokine Genes

Background: The change of treatment led to change in the course of juvenile idiopathic arthritis (JIA). The dependence of the course and possibilities of JIA therapy on genetic features has not been studied enough.

Purpose: Assess the correlation of allelic polymorphism of the genes and features of the course of JIA.

Methods: An analysis of medical documentation of 97 JIA patients. All patients was determined IL in the blood serum by electrochemiluminescence method, the PCR method identified genes IL-6(G-174C), TNF(G308A), and folate metabolism genes (MTHFR) in 30 their buccal scrapings.

Results: There were 10.6% of sJIA, 31.9% oJIA, 8.5% RF+pJIA, 29.8% RF-pJIA, 12.8% eA and PsA. It was revealed that the number of affected joints increased with age (to 7.7±1.8 in adolescents). The highest activity observed in 10-14y, maximum in sJIA. 37.1% had an unfavorable course (UFC) of the disease, because the clinic is specialized. The IL-6 CC phenotype was found in 30%, GC (norm) 46.7%, GG 23.3% (in UFC CC 66%, p<0.05). There is no clear correlative dependence of the IL-6 and peculiarities of allelic polymorphism. UFC-patients with the GC often experienced osteoporosis (r=0.8), bone erosion (r=0,6); with GG sacroiliitis (r=0.8), with CC uveitis (r=0.2). TNF-GG-phenotype(norm) was found in 67%, GA in 33%. There was a weak correlation of serum TNF-α with the heterozygosity (r=0.42) and GG (r=-0.43). 40% of children with the GA-phenotype had an UFC. Allelic polymorphism MTHFR occurred in 100% cases. 30% of them (with 2-4 polymorphisms) examined had an insufficient response to methotrexate therapy. MTHFR(A66G)GG-phenotype was most common for PsA-patients, MTHFR(A1298C)AA - sJIA. Patients with uveitis had MTHFR(C677T)CC (r=-0.65). ANA-positivity closely correlated (r=1.0) with the MDR1(C3435T)GG.

Conclusion: The study of the genes IL-6, TNFα and MTHFR may suggests some features of the course of the disease, which may allow optimizing and individualizing its treatment.