The role of the immune response mediator genes polymorphism in the predisposition to juvenile idiopathic arthritis

Abstract

Objective ― The aim of the work was to study the contribution of the immune response mediator genes polymorphism (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) to the formation of the predisposition to juvenile idiopathic arthritis (JIA) and its clinical variants. Material and Methods ― The JIA group included 330 patients and the control group – 342 volunteers without autoimmune diseases from the Republic of Bashkortostan, Russia. Genotyping was conducted by the real-time polymerase chain reaction. Results ― Taking into account the differences by sex, it was established, that the alleles/genotypes of the TNFA rs1800629, LTA rs909253, IL2-IL21 rs6822844, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype are associated with the development of JIA as a whole (p<0.05); alleles/genotypes of the LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype – with some of JIA clinical variants (p<0.05). Conclusion ― In this work, the relationship of the alleles, genotypes and haplotypes of a number of the immune response mediator genes polymorphic loci with the risk of the development of JIA and its clinical variants was established. Specific associations were observed for girls and boys, which indicates the existence of sexual dimorphism in the JIA pathogenesis.

Interaction Of Immune Response Mediator Genes In A Predisposition To Juvenile Idiopathic Arthritis

“…When analyzing the results, for a number of loci, we found no statistically significant associations with the development of JIA (in general). Taking into account the data on the presence of corresponding relationships presented in some publications, we suggested that the observed inconsistency was probably related to specific features of the samples, clinical heterogeneity, and sexual dimorphism of JIA [5]. However, a growing body of research suggested that the lack of association in some cases could be caused by an isolated examination of the polymorphic loci variants [6][7][8][9].…”

“…This study was carried out as an extension of our earlier research, using the results of genotyping obtained in that previous study; the sample characteristics (330 JIA patients and 342 volunteers from the Republic of Bashkortostan, Russia) and the parameters of molecular genetic analysis were described in detail in the preceding publication [5].…”

“…To date, a large number of genetic determinants has been analyzed, including polymorphic loci of the immune response mediator genes (such as genes of interleukins (ILs) and their receptors (ILRs), tumor necrosis factor-alpha (TNF-α), lymphotoxin alpha (LT-α), macrophage migration inhibitory factor (MIF), nuclear factor kappa B (NF-κB), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), peptidyl arginine deiminase 4 (PAD4)). However, the results are often contradictory [3][4][5].…”

“…We have previously studied the association of separate variants of 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, PADI4 rs2240336), as well as of the haplotypes of TNFA rs1800629 and LTA rs909253 polymorphic loci, with the development of JIA and its clinical variants [5]. When analyzing the results, for a number of loci, we found no statistically significant associations with the development of JIA (in general).…”

“…These mediators could significantly modify -weaken or enhance -the effects of each other. For instance, the interrelation has been reported between the levels of cytokines and other factors that were presumably involved in the JIA pathogenesis [3,5,[12][13][14][15][16][17][18][19].…”