SARS-CoV-2 is a global threat that influenced healthcare systems around the world. This virus caused an infection in humans with different clinical signs and syndromes, severity, and mortality. The key components of the COVID-19 molecular pathogenesis are coronavirus entry and replication, antigen presentation, humoral and cellular immunity, cytokine storm, coronavirus immune evasion. The analysis of recent literature displayed possible molecular targets in the key components of the COVID-19 pathogenesis. Some of these targets might have gene polymorphisms that influenced the COVID-19 course. Unfortunately, several findings are still putative or extrapolated from SARS and MERS experimental investigations or clinical trials. We systematised original data about gene polymorphisms of possible molecular targets and associations with the COVID-19 course. Most data were obtained for angiotensin-converting enzymes 1 and 2, TMPRSS2 gene polymorphisms. Only a few results were found for gene polymorphisms of adhesion molecules, interferon system components, cytokines, and transcriptional factors, oxidative stress and metabolic molecules, as well as haemocoagulation. Understanding the host gene variability and its associations with COVID-19 can provide insights into the disease pathogenesis, individual susceptibility to SARS-CoV-2 infection, severity, complications, and mortality prognosis for the disease. Besides, these data might help in the identification of appropriate targets for intervention.
Introduction The severity of SARS-CoV-2 induced coronavirus disease 19 (COVID-19) depends on the presence of risk factors and the hosts' gene variability. There are preliminary results that gene polymorphisms of the renin-angiotensin system can influence the susceptibility to and mortality from COVID-19. Angiotensin II type 1 receptor (AT1R) might be a gene candidate that exerts such influence. The aim of this study was to elaborate on the association between A1166C at1r polymorphic variants and the susceptibility to and severity of COVID-19 in the Ukrainian population. Methods The study population consisted of the Ukrainian population (Poltava region) with COVID-19, divided into three clinical groups in accordance with oxygen requirement: patients without oxygen therapy ( n = 110), with non-invasive ( n = 136) and invasive ( n = 36) oxygen therapy. The A1166C polymorphism of the at1r was determined by polymerase chain reaction with subsequent restrictase analysis. In an attempt to better explain the role of the A1166C at1r polymorphism we compared its association with COVID-19, essential hypertension ( n = 79), renoparenchimal hypertension ( n = 30) and dyscirculatory encephalopathy ( n = 112). The data for this comparison were obtained by meta-analysis. Results We observed significant differences in the frequency of AA, AC and CC genotypes in the groups of COVID-19 patients with non-invasive and invasive oxygen therapy in comparison with control subjects as well as in the frequency of combined AC + CC genotype between the groups of COVID-19 patients with any types of oxygen therapy and patients without oxygen therapy. The frequency of the 1166C allele was higher in COVID-19 patients with invasive oxygen therapy (OR = 2.06; CI (1.20–3.53); p = 0.013). We obtained important results indicating that there were no differences between the frequency of at1r polymorphisms in patients with cardiovascular disease and severe COVID-19 with invasive oxygen therapy as well as those who died due to COVID-19. Conclusion Our study indicated the presence of an association between the A1166C at1r polymorphisms and the severity of COVID-19 in the Ukrainian population. It seems that in carriers of 1166C at1r , the severity of COVID-19 and oxygen dependency is higher as compared to the A allele carriers, possibly, due to cardiovascular disorders.
Исследование однонуклеотидных полиморфизмов Toll-подобных рецепторов имеет важное прикладное и теоретическое значение для раскрытия механизмов формирования особенностей иммунитета и его коррекции. Целью работы было изучение имеющейся частоты полиморфных вариантов 2258G/A гена TLR2 (rs5743708) и 896A/G (rs4986790), 1196С/Т (rs4986791) гена TLR4 и оценка связи с состоянием здоровья практически здоровых лиц. Материалы и методы: в исследовании приняли участие 114 человек белой расы, проживающих в г. Полтава или Полтавской области минимум 2 года, которым проводился сбор анамнестических данных, данных объективного и клинического состояний. Определение полиморфных участков генов TLR2 (rs5743708) и TLR4 (rs4986790, rs4986791) осуществлялся методом полимеразной цепной реакции (ПЦР) с последующим анализом длин рестрикционных фрагментов продуктов ПЦР. Результаты распределения генотипов полиморфных вариантов 2258G/A гена TLR2 (rs5743708), 896A/G гена TLR4 (rs4986790), 1196С/Т гена TLR4 (rs4986791) соответствовали теоретически ожидаемым при равновесии Харди-Вайнберга (χ2=0,02, р=0,99; χ2=0,29, р=0,86; χ2=1,46, р=0,48, соответственно). При сравнении наличия отдельных клинических проявлений, которые были отмечены при опросе, с наличием в генотипе полиморфных аллелей была установлена достоверная связь между наличием аллеля А в генотипе при полиморфном варианте гена TLR2 (rs5743708) с ревматизмом (р = 0,05), пиелонефритом (р = 0,05) и у лиц, имевших вредную привычку – курение (р = 0,04).
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