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

A Genome-Wide Analysis of Populations from European Russia Reveals a New Pole of Genetic Diversity in Northern Europe

Peer reviewe

Взаимосвязь полиморфизмов генов ренин-ангиотензиновой системы с показателями интенсивности кариеса зубов

Данные о взаимосвязях состояния органов и тканей рта с функционированием системы гемодинамики интересны при изучении заболеваний тканей пародонта, их корреляций с общесоматической патологией, но зачастую исследования проводятся без учета молекулярно-генетических детерминант. Цель работы – установление взаимосвязи между полиморфизмами Т704С, С521Т гена ангиотензиногена (AGT), А1166С гена рецептора 1-го типа ангиотензина II (AGT2R1) и показателями интенсивности кариеса зубов у молодых жителей Европейского Севера России. Материалы и методы. Группа исследования состояла из 57 практически здоровых юношей и девушек (средний возраст – 18,2 года; доверительный интервал – 17,9–19,4 года), постоянно проживающих на территории Архангельской области. Проводили генотипирование изучаемых полиморфизмов методом пиросеквенирования, устанавливали частоты встречаемости аллелей и генотипов. Уровень ангиотензина II в плазме крови определяли иммуноферментным методом. Рассчитывали индекс КПУ (сумма кариозных, пломбированных и удаленных зубов) и выявляли степень интенсивности развития кариеса зубов у людей с наличием и отсутствием мутантных аллелей по каждому варианту генов. Результаты. Наличие мутантных аллелей вариантов генов AGT и AGT2R1 в геноме молодых людей сопровождалось увеличением индекса КПУ, однако статистически значимое увеличение отмечено только в варианте Т704С. Уровень ангиотензина II у молодых людей статистически значимо не различался по полу, но наблюдалась тенденция к его повышению при наличии в генотипе мутантных аллелей всех изучаемых генов. Среди носителей мутантного аллеля С варианта Т704С гена AGT чаще встречались люди с декомпенсированной степенью интенсивности кариеса, а у носителей мутантного аллеля Т варианта С521Т гена AGT наблюдалось увеличение частоты субкомпенсированной степени. У обладателей мутантного аллеля С варианта А1166С гена AGT2R1 зарегистрирован рост частоты встречаемости компенсированной степени интенсивности кариеса при незначительном снижении частот субкомпенсированной и декомпенсированной степеней

ADMIXTURE clustering of individuals from the populations studied.

<p>Results obtained at K = 2 to 5 are shown. Each individual is represented by a vertical line composed of colored segments, in which each segment represents the proportion of an individual’s ancestry derived from one of the K ancestral populations. Individuals are grouped by population (labeled on the bottom of the graph). In addition to populations used in principal component analysis, a Chinese sample (Han Chinese from Beijing <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone.0058552-The1" target="_blank">[22]</a>) was included. The results at K = 5 are also accompanied by average ancestral proportions by population (*). Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Principal component analysis of the combined autosomal genotypic data of individuals from Russia and seven European countries (Finnland, Estonia, Latvia, Poland, Czech Republic, Germany [5] and Italia [22]).

<p>The first two PCs are shown. The color legend for the predefined population labels is indicated within the plot. Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

F_ST values and the number of SNPs with significant differences in allele frequencies between the populations from Russia^*.

*<p>Pairwise F_ST values are indicated below the diagonal and the number of SNPs is indicated above it. The abbreviations of populations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Principal component analysis of the autosomal genotypic data of individuals from European Russia.

<p>The first two PCs are shown. Each individual is represented by a sign and the color label corresponding to their self-identified population origin. Population designations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p

Summary of ROH statistics of 16 European populations.

*<p>ROH calculated without the thresholds for SNP density and length of the gaps along a ROH tract. The abbreviations of populations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058552#pone-0058552-g001" target="_blank">Figure 1</a>.</p