Background Juvenile idiopathic arthritis (JIA) is heterogenous group of diseases and it is most common rheumatic disease in children. Inflammatory cytokines and their regulatory gene polymorphisms are important in the pathogenesis of JIA. Interleukin 6 (IL-6) is significant in inflamation  whereas IL-10 has anti-inflammatory activity . Protein tyrosine phosphatase non-receptor 22 (PTPN22) has impact on T and B cell regulation and activation . One single nucleotide polymorphisms (SNP) substitution within certain gene can affect cytokine production, T and B cell regulation, inflammatory processes and disease outcome.
Objectives To determine the association of IL-6, IL-10 and PTPN22 gene SNP with JIA.
Methods All 40 JIA patients (19 seronegative and 5 seropositive polyarthritis, 10 persistent and 6 extended oligoarthritis) and 20 healthy controls were determined for IL-6 gene promoter polymorphisms in –174GG, -174GC and –174CC positions, IL-10 gene promoter SNP in -(1082A), -(819T) and -(592A)positions, as well as the PTPN22 gene C1858T polymorphism for genotypes T/T and T/T + C/T. The sample genetic analysis was performed using real-time polymerase chain reaction (RT-PCR) for DNA tipping technique with TaqMan SNP genotyping probes (QuantiFast Probe RT-PCR Kit Plus Applied Biosystems). Each potential SNP genotype distribution was compared between the different types of JIA and control group using chi-square test and Fisher’s exact test.
Results We found significant differences in IL-6 -174GC genotype distribution between JIA patients and controls (OR=2,05; p<0,031). Among JIA subtypes IL-6 SNP in -174GG and -174CC positions has no significant differences (p<0,36), but –174GC position was more common in seronegative polyarthritis JIA patients (OR=0,41, p<0,005). Certain haplotypes GCC, ACC and ATA for three IL-10 promoter SNPswere investigated. JIA patients compared to controls, demonstrated significantly higher IL-10 ATA/GCC and GCC/GCC haplotype distribution (p=0,005 and p=0.02). Comparing IL-10 promoter SNPs between JIA subtypes, no significant differences were found (p=0,36), which is probably due to the small number of patients. The PTPN22 C1858T SNPs for C/T genotype was significantly higher in JIA group (OR=1.36, p<0,035). Comparing PTPN22 C1858T SNPs genotypes between JIA subtypes no significant differences were found.
Conclusions 1. IL-6 SNP –174G/C was more common in JIA seronegative polyarthritis. 2. JIA patients demonstrated higher IL-10 ATA/GCC and GCC/GCC haplotypes distribution 3. PTPN22 C1858T C/T genotype was seen more common in JIA. 4. To obtain more accurate data on the regulatory cytokine gene polymorphisms in the pathogenesis of JIA, additional studies are need.
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Disclosure of Interest None Declared