Interaction of immune response mediator genes in a predisposition to juvenile idiopathic arthritis

摘要

Background/objective - The goal of our study was to investigate the role of interaction between the polymorphic loci of immune response mediator genes (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, and PADI4 rs2240336) in the formation of a genetic predisposition to juvenile idiopathic arthritis (JIA).Material and Methods - The study involved 330 JIA patients and 342 volunteers from the Republic of Bashkortostan. Genotyping was conducted via the real-time polymerase chain reaction. The gene-gene interactions were studied using the multifactor dimensionality reduction algorithm.Results - In general analysis, the best model of gene-gene interaction in JIA was a combination of IL1B rs16944 -IL10 rs1800872 - NFKB1 rs28362491 - PADI4 rs2240336 polymorphic loci. However, after gender-based stratification the best results were obtained when examining the combinations of IL6 rs1800795 -PADI4 rs2240336 loci in girls and of IL10 rs1800872 -IL6 rs1800795 -IL2RA rs2104286 loci in boys. Within all of these models, the genotype combinations associated with both augmented and reduced JIA risks were identified (taking into account gender-specific differences). Conclusion - The results of our study implied that an important role in the formation of a predisposition to JIA is played by gene-gene interactions of IL1B rs16944, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, NFKB1 rs28362491, and PADI4 rs2240336 polymorphic loci (taking into account gender-specific differences).