Genetic susceptibility to juvenile idiopathic arthritis in the Belarusian population: gene-gene interactions analysis

Abstract

Background. GWASs revealed a huge amount of candidate genes for juvenile idiopathic arthritis (JIA) susceptibility. Individual SNP analysis has restrictions as an effect of each substitution may be too subtle to be detected but their interactions may significantly contribute to disease susceptibility. Materials and methods. 118 patients diagnosed with JIA and 202 controls were included into the study. The study was aimed to estimate interactions between SNPs of the immune and inflammatory responses genes: RUNX3 (rs11249215), RUNX1 (rs9979383), STAT4 (rs7574865), TRAF1/C5 (rs3761847), MIF (rs755622), CTLA4 (rs5742909, rs231775), PTPN2 (rs2542151) and to reveal their effects on the JIA susceptibility. SNPs were genotyped using PCR-RFLP and Real-time PCR. Multifactor dimensionality reduction analysis was performed using MDR 3.0.2 software. Results. RUNX3, STAT4 and PTPN2 polymorphisms were associated with systemic arthritis, RF- polyarthritis and oligoarthritis respectively. Interaction of CTLA4 (rs5742909, rs231775), TRAF1/C5 (rs3761847), RUNX1 (rs9979383), PTPN2 (rs2542151) SNPs is shown to be a risk factor for JIA (p = 0.0099). Conclusion. Some of the SNPs studied are associated with distinct JIA subtypes. MDR analysis identified a statistically significant high-order interaction of five polymorphisms which collectively may contribute to JIA genetic susceptibility in the Belarusian population.