Polymorphism of pro-inflammatory cytokine genes in acute intestinal infections

Abstract

Acute intestinal infections are widespread and hold the second place among infectious diseases, giving way solely to respiratory diseases. In this regard, much attention has been paid to examining acute intestinal infections, including immunopathogenetic mechanisms. And since proinflammatory and antiinflammatory cytokines play an important role in development of inflammatory reactions affecting disease severity and outcome, it becomes reasonable to study polymorphism of genes governing production of related molecules. Thus, the aim of our study was to examine the polymorphism in the IL-1β Т31С and IL-2 T330G genes; such mutations were characterized by nucleotide replacement affecting the gene promoters, which influenced production rate and level of the relevant cytokines. There were enrolled 108 patients with acute intestinal infections comprising main group as well as 94 apparently healthy subjects in the control group. Genomic DNA was isolated from the whole blood leukocytes by using a DNA-express-blood reagent, followed by conducting amplification reaction with two pairs of allele-specific primers. The polymorphism in the IL-1β, IL-2 genes was determined by PCR with primers purchased from Litech LLC (St. Petersburg). Data processing was carried out by using the statistical Statistica 6 suite software. While assessing the carriage rate of IL-1β T31C gene polymorphic markers by using the multiplicative inheritance model in both groups, the prevalence of the normal T allele and, respectively of the —31TT and —31TC genotypes with OR = 1.83 and an interval of 1.04—3.22 (χ2 = 6.35, p = 0.04, df = 2) was found, which allowed us to identify a relationship between the carriage of IL-1β в gene heterozygous variant and potentially elevated risk of AII. Regarding the IL-2 T330G gene, it was found that pathological G alleles was more markedly abundant in patients with acute intestinal infections compared to control group. Analyzing diverse IL-2 T330G carriage rate in patients with acute intestinal infections revealed that carriers of the TG heterozygous variant predominated — 56.48% (χ2 = 17.75, F = 0.000031), whereas pathological genotype GG was found in 13.89% (χ2 = 12.31, F = 0.000663, p < 0.05), with high probability of the relationship between carriage of these genotypes and a risk of disease development (OR — 3.63 [1.97—6.68] and OR — 6.91 [2.12—22.59]). Hence, the carriage of polymorphic variants of the IL-1β T31C and IL-2 T330G genes was associated with elevated risk of developing AII in case of infection with pathogenic microorganisms.