ПОЛИМОРФИЗМ ГЕНОВ TOLL-ПОДОБНЫХ РЕЦЕПТОРОВ КАК ВОЗМОЖНЫЙ ФАКТОР ПРЕДРАСПОЛОЖЕННОСТИ К РАЗВИТИЮ ТУБЕРКУЛЕЗА

Abstract

The objective of the study : to detect genotypes and frequency of gene alleles of Toll-receptors (Arg753Gln – for TLR2; Phe412Leu – for TLR3; Asp299Gly – for TLR4; Ser249Pro – for TLR6) among respiratory tuberculosis patients in Zabaykalsky Kray. Subjects and methods . The distribution of genotypes of allele variants of Toll-receptors genes was analyzed in 120 respiratory tuberculosis patients and 30 healthy volunteers with a compatible gender and age distribution. Genomic DNA was isolated from leukocytes of the whole blood. In order to detect polymorphic variants of Toll-receptors genes, real-time PCR was used. The distribution of genotypes as per investigated polymorphic loci was tested for relevance using Hardy – Weinberg equilibrium. The frequency of genotype distribution in the groups was compared by Pearson's chi-square test with Yates's correction for continuity using 4-field contingency tables. The decision of the association between genotypes and the disease was made based on the value of the odds ratio with 95% of confidence intervals. Additionally, to confirm and analyze the correlation force of genotypes and development of tuberculosis based on the principle of mutual contingency, φ test (Kramer test, Chuprov test) was calculated. Results. Polymorphism of TLR2, TLR3 and TLR6 genes predispose the development of tuberculosis. The following genotypes make the biggest contribution to the formation of predisposition to tuberculosis: Asp/Asp genotype of TLR4 gene (Asp299Gly), Ser/Ser polymorphism of TLR6 gene (Ser249Pro), heterozygous Asp/Gly of TLR4 gene (Asp299Gly) and mutation Pro/Pro polymorphism of TLR6 gene (Ser249Pro). The protective effect against the development of tuberculosis is related to carriage of homozygous Arg/Arg genotype of TLR2 polymorphism, homozygous Phe/Phe genotype of TLR3 gene and heterozygous Ser/Pro polymorphism of TLR6 gene.