INTERLEUKIN 1 AND INTERLEUKIN 4 GENES POLYMORPHISM ASSOCIATED WITH EARLY AND PRESCHOOL AGE CHILDREN SENSITIZATION TO STREPTOCOCCUS PYOGENES

Abstract

Background. Streptococcus pyogenes infection and sensitization to its antigens is considered to be an unfavorable factor for the induction of rheumatic pathology. The search for genetic predictors of rheumatic diseases in general, and sensitization to S. pyogenes, in particular, is of high relevance in modern medicine.Objective. To study the associations between interleukin 1 and interleukin 4 gene polymorphisms and the development of sensitization to antigens of S. pyogenes in toddlers and preschool children.Materials and methods. 771 children aged 2–6 years with recurrent acute respiratory tract infections treated by allergist-immunologist and otorhinolaryngologist were included in the study. Antibodies against S. pyogenes were determined by ELISA using commercial kits “Immunoteks” (Stavropol, Russia) in all children. Children with IgG immune response to S. pyogenes were assigned to the study group (n = 306), whereas children without this response were assigned to the control group (n = 465). Both groups underwent gene typing of IL1B (+3953, C→T, rs 114634), IL1Ra (VNTR, intron 2, 89 bp) and IL4 (VNTR intron 3, 70 bp) gene polymorphisms in the Laboratory for Pharmacogenomics, ICBFM SB RAS. The data were processed using routine statistical methods for genetic analysis and the statistical software package Statistica 6.0. There were no deviations from Hardy–Weinberg equilibrium across all loci, suggesting validity of association studies between individual and combined genotypes and sensitization to antigens of S. pyogenes.Results. Positive association between sensitization to antigens of S. pyogenes and individual genotypes have been found: IL1B (+3953, C→T)*C,T (52.6% in the study group vs. 39.8% in the control group, p = 0.001; OR = 2.02; CI(99%) 0.47–5.93), IL1Ra (VNTR, intron 2, 89 bp)*2r,5r (7.19% in the study group vs. 1.29% in the control group, p = 0.001; OR = 5.59; CI(99%) 1.58–19.77), IL4 (VNTR intron 3, 70 bp)*2r,2r (6.86% in the study group vs 3.01% in the control group, p = 0.05; OR = 2.34; CI(99%) 0.66–8.29); as well as for combined genotypes: IL1B (+3953, C→T)*C,C / IL1Ra (VNTR, intron 2, 89 bp)*2r,4r / IL4 (VNTR intron 3, 70 bp)*2r,2r (OR = 46.15); IL1B (+3953, C→T)*T,T / I-1Ra (VNTR, intron 2, 89 bp)*4r,4r / IL4 (VNTR intron 3, 70 bp)*2r,3r (OR = 8.82) and IL1B (+3953, C→T)*C,T / IL1Ra (VNTR, intron 2, 89 bp)*2r,2r / IL4 (VNTR intron 3, 70 bp)*3r,3r (OR = 7.23). Conclusion. High odds ratio (OR = 46.15) for IL1B (+3953, C→T)*C,C / IL1Ra (VNTR, intron 2, 89 bp)*2r,4r / IL4 (VNTR intron 3, 70 bp)*2r,2r suggests that combined genotype is a main marker of sensitivity and impaired immune tolerance to S. pyogenes in toddlers and preschool children. Thus, this study has confirmed the association between gene polymorphisms, and pro-inflammatory and proallergic cytokines, and autoimmune and allergic diseases.