The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance

Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections

Association of single nucleotide polymorphisms of <i>TLR2</i>, <i>TLR4</i> and <i>TLR9</i> with atopic dermatitis

Toll-like receptors (TLRs) are the most studied among all Pattern Recognition Receptors, the main function of which is to initiate innate immune response by recognizing pathogen-associated molecular patterns of various microorganisms on the skin surface. TLR-mediated recognition plays an important role in linking innate and adaptive immunity that ultimately leads to the production of key cytokines, chemokines and antimicrobial peptides. Today, there is growing interest in research on single nucleotide polymorphisms (SNPs) in TLR genes and its influence on susceptibility to inflammatory disease, including atopic dermatitis. The aim of the research was to study the association of the rs5743708 gene polymorphism in the TLR2 gene, the rs4986791 gene polymorphism in the TLR4 gene and the rs352140 gene polymorphism in the TLR9 gene with the risk of developing severe cases of AD. A total of 100 patients with AD were included in the study (38 male and 62 female). The age range was from 18 to 65 years old. All participants were divided into 2 groups according to the SCORAD index (SCORing Atopic Dermatitis). The control group included 72 volunteers over 18 years old. The results of our study showed a statistically significant difference between the moderate AD group and healthy controls in the rs352140 gene polymorphism in the TLR9 gene (Figure 1). The frequency of the GG genotype of SNP rs352140 in TLR9 was 0.169 in the AD group versus 0.329 in the control group (p &lt; 0.05; OR = 0.42; 95% CI = 0.18-0.97).In conclusion, the results of our study showed that the TLR9 rs352140 gene polymorphism may be linked to an increased risk of atopic dermatitis. Moreover, it was found that the GG genotype of SNP rs352140 in TLR9 can be used as a predictor of the risk of developing moderate AD