Abstract
The aim of the research is to establish an association between Arg753Gln polymorphism of TLR-2 gene, Leu412Phe of TLR-3 gene, Asp299Gly of TLR-4 gene and susceptibility to inflammatory diseases of the upper and lower respiratory tract and the complicated forms of АRI development. Materials and methods . 98 healthy subjects distributed according to the genotype of TLR-2, TLR-3, TLR-4 were enrolled in the study of association between Arg753Gln polymorphism of TLR-2, Leu412Phe of TLR-3 and Asp299Gly of TLR-4 genes and inflammatory diseases of the upper and lower respiratory tract. The polymorphic site of TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly genotyping was performed by polymerase chain reaction using oligonucleotide primers. The relative risk of the disease and complications development was estimated using the odds ratio with 95 % confidence interval. The statistical significance of differences in qualitative characteristics was evaluated using Fischer's exact test. Results. It has been revealed that individuals with polymorphic TLR-2, TLR-3 and TLR-4 genes have an increased susceptibility to АRI with frequent episodes during the year that are complicated by lower respiratory tract inflammation as well as chronic inflammatory diseases of the upper respiratory tract. It has been shown that the risk of bronchitis and pneumonia development in АRIs is higher in subjects with polymorphic genotypes of TLR-2, TLR-3 and TLR-4 as compared to the carriers of normal alleles distribution: 2.9 times with Leu/Phe genotype of TLR-3, 20.0 times with Phe/Phe of TLR-3 and 12.8 times with combinations of polymorphic genotypes of TLR-2, TLR-3, TLR-4. Conclusions. The results of the study indicate that the presence of single-nucleotide polymorphisms TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly is the marker of high susceptibility to respiratory diseases. Individuals with polymorphic status of TLR-2, TLR-3 and TLR-4 genotypes have an increased susceptibility to inflammatory diseases of the upper and lower respiratory tract with АRI frequency of 4 or more episodes during the year.
Highlights
Acute respiratory infections (ARIs) are the most common infectious diseases affecting all age groups. 10–14 million people in Ukraine suffer from ARIs every year, which accounts for 25–30 % of overall morbidity and about 75–90 % of infectious diseases incidence in the country
According to the study results, individuals with polymorphic genotypes in Toll-like receptors (TLRs)-2, TLR-3 and TLR-4 showed a high susceptibility to ARIs with frequent episodes during the year which were complicated by inflammatory processes of the lower respiratory tract (LRT), as well as chronic inflammatory diseases of the upper respiratory tract
It should be noted that one third (30.6 %) of the subjects with normal distribution of TLR gene alleles suffered from ARI infrequently – once every 2 years or less, which was practically not observed in individuals with polymorphic variants of TLR-2, TLR-3 and TLR-4 genes
Summary
Acute respiratory infections (ARIs) are the most common infectious diseases affecting all age groups. 10–14 million people in Ukraine suffer from ARIs every year, which accounts for 25–30 % of overall morbidity and about 75–90 % of infectious diseases incidence in the country. Acute respiratory infections (ARIs) are the most common infectious diseases affecting all age groups. 10–14 million people in Ukraine suffer from ARIs every year, which accounts for 25–30 % of overall morbidity and about 75–90 % of infectious diseases incidence in the country. Understanding the mechanisms of the respiratory tract nonspecific protection from infectious agents becomes of particular relevance. The variety and abundance of infectious pathogens, contacted by the respiratory tract mucous membrane involve the existence of complex multifactorial induction of the respiratory tract local protection. Toll-like receptors (TLRs) are the central link of the multi-level system for recognition of pathogen-associated molecular structures, whose activation when the respiratory tract is infected leads to the expression of genes involved in the inflammatory process regulation, the innate mechanisms of protection against infectious agents and acquired immunity
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