Биохимические, молекулярно-генетические и клинические аспекты COVID-2019

 The 2020 coronavirus infection pandemic has potentiated a large number of studies in the world on the etiopathogenesis, clinical and morphological manifestations of COVID-2019 infection. This review presents biochemical, molecular genetic and clinical aspects of COVID-2019.  Пандемия коронавирусной инфекции в 2020 г. потенцировала проведение большого числа исследований в мире в области этиопатогенеза и клинико-морфологических проявлений  COVID-2019. Представлены биохимические, молекулярно-генетические и клинические аспекты COVID-2019.

Non-alcoholic fatty liver disease and metabolic liver dysfunction in the new coronavirus infection COVID-19

Our study aimed to explore associated non-alcoholic fatty liver disease (NAFLD) and metabolic liver dysfunction influence on the severity of the new coronavirus infection COVID-19. Material and methods. The study design was a cross-sectional study. The research included 215 patients (39.50 % of men) aged 26–60 years who had undergone a new coronavirus infection COVID-19 at least two months ago. Participants were divided into three groups by severity of infection: mild (n = 99), moderate and severe (n = 116) by anamnesis. Hepatic steatosis index (HIS), body mass index (BMI), waist circumference, alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, systolic and diastolic pressure were calculated and abdominal ultrasound examination was done. Results. In the group with moderate and severe course of COVID-19, the proportion of patients diagnosed with NAFLDaccording to the HSI index was significantly higher compared to patients with mild coronavirus infection. Patients with mild COVID-19, who were diagnosed with NAFLD, had higher alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, BMI, systolic and diastolic pressure, waist circumference compared to patients without NAFLD. Similar differences persisted for patients with moderate and severe course. With the step-by-step exclusion of cardiometabolic parameters from the logistic regression model, the triglyceride content and BMI retained association with steatohepatosis according to ultrasound data, regardless of severity. When creating a similar model for the HSI index, significant correlation was shown for alanine aminotransferase activity in patients with mild COVID-19, for alanine aminotransferase activity and BMI – in patients with moderate and severe COVID-19. Conclusions. Patients with NAFLD have a more severe course of COVID-19. In addition, associations of the severity of COVID-19 with a combination of NAFLD and other cardiometabolic changes in the body, such as arterial hypertension, obesity, dyslipidemia, were revealed

Association of lipid profile parameters, atherogenic index of plasma, anthropometric parameters with the severity of the COVID-19 course in Novosibirsk women

Background: Our study aimed to assess the relationship between the parameters of the lipid profile, atherogenic index of plasma (AIP), anthropometry influence with the severity of the new coronavirus infection COVID-19 in women. Material and methods. The study design was a cross-sectional study. The research included 138 women aged 29–82 years who had undergone a new coronavirus infection COVID-19 at least two months ago. Participants were divided into three groups by severity of infection: mild (n = 61), moderate (n = 70) and severe (n = 7). Body mass index, waistline and hip circumference, waistline circumference to hip circumference index, total cholesterol, triglycerides, HDL, LDL, AIP were calculated. Statistical processing of the obtained results was carried out using the SPSS software package (version 20.0) using the Mann-Whitney test, univariate logistic regression analysis, Pearson chi-squared test. Results. The levels of HDL-cholesterol were significantly lower in group 3 compared with the level of HDL-cholesterol in women in group 2 (p2-3 = 0.046). BMI was higher in the moderately severe group compared to the mild one (26.32 [23.305; 30.4] versus 28.78 [24.72; 34.77], p1-2 = 0.026). Hip circumference was higher in patients with severe COVID-19 than in patients with mild course (104 [98; 112] versus 114 [109.5; 126], p1-3 = 0.039), AIP was higher in women with severe course compared to women with moderate and mild course (p1-3 = 0.043, p2-3 = 0.04). The results of the logistic regression analysis showed that the moderate course of COVID-19 is associated with BMI (OR = 1.09, 95 % CI 1.019–1.166, p1-2 = 0.012), and the severe course with WC (OR = 1.041, 95 % CI 1.001–1.084, p1-3 = 0.046), AIP value ≥ 0.11 (OR = 13.824, 95 % CI 1.505–126.964, p1-3 = 0.02; OR = 11,579, 95 % CI 1,266–105,219, p2-3 = 0.03) and HDL level < 40 mg/dl (OR = 14,750, 95 % CI 2,317–93,906, p1-3 = 0.004; OR = 8,000, 95 % CI 1,313– 48,538, p1-3 = 0.024). Conclusion. Patients from the group with moderate and severe course of the new coronavirus infection have higher body mass index, hip circumference, AIP, lower HDL values. The chance of a moderate course of COVID-19 is associated with an increased BMI value, and a severe course with WC, AIP ≥ 0.11 and HDL level < 40 mg/dl

Распространенность заболеваний и патологических состояний у молодых людей до 45 лет с абдоминальным ожирением в Сибири

Aim. To study the prevalence of abdominal obesity in young people aged 25–44 years in Novosibirsk, as well as the prevalence of diseases and pathological conditions in individuals with abdominal obesity.Materials and methods. We conducted a cross-sectional, population-based study of the population of Novosibirsk aged 25–44 years. The screening examined 1,415 people, including 670 men and 745 women. For all individuals, we evaluated the presence of such conditions as abdominal obesity (AO), arterial hypertension (AH), increased body mass index (BMI), coronary heart disease (according to validated epidemiologic and functional criteria with ECG findings classified according to the Minnesota Code), diabetes mellitus (DM), reduced glomerular filtration rate (GFR), chronic bronchitis (CB), increased blood levels of total cholesterol (hypercholesterolemia) and lowdensity lipoprotein (LDL) cholesterol (hyper-LDL-cholesterolemia).Results. The prevalence of AO in the population of Novosibirsk aged 25–44 years was 42.4%: in men – 42.7%, in women – 42.1%. We found that AO had a significant direct effect on the development of AH (odds ratio (OR) = 2.550, 95% confidence interval (CI) 1.899–3.422, p = 0.0001), CB (OR = 1.830, CI 1.326–2.527, p = 0.0001), hypercholesterolemia (OR = 1.486, CI 1.193–1.851, p = 0.0001), hyper-LDL-cholesterolemia (OR = 1.527, CI 1.222–1.907, p = 0.0001) and a reverse effect on reduced GFR (OR = 0.603, CI 0.427–0.852, p = 0.004). In the male population under 45 years of age, AO had a significant direct effect on the development of AH, CB, hypercholesterolemia, and hyper-LDL-cholesterolemia. In the female population under the age of 45, AO had a significant direct effect on the development of DM, AH, CB, and hyper-LDL-cholesterolemia and a reverse effect on the reduced GFR development.Conclusion. Therefore, in the young Siberian population under 45 years of age, abdominal obesity is associated with the development of common diseases and pathological conditions. Цель – изучение распространенности абдоминального ожирения (АО) в популяции молодых людей 25– 44 лет г. Новосибирска, а также распространенности терапевтических заболеваний и патологических состояний у лиц с АО.Материалы и методы. Проведено одномоментное популяционное обследование населения 25–44 лет г. Новосибирска. На скрининге обследованы 1 415 человек, из них 670 мужчин (47,3%) и 745 женщин (52,7%). Беременные и женщины в декретном отпуске не включались в исследование. У обследуемых оценивалось наличие таких заболеваний и патологических состояний, как АО, артериальная гипертензия (АГ), повышенный индекс массы тела, ишемическая болезнь сердца (по валидизированным эпидемиологическим и функциональным критериям с расшифровкой электрокардиограммы по Миннесотскому коду), сахарный диабет (СД), сниженная скорость клубочковой фильтрации (СКФ), хронический бронхит (ХБ), повышенный уровень в крови общего ХС (гиперХСемия), повышенный уровень в крови ХС-ЛНП (гиперХС-ЛНПемия).Результаты. Распространенность АО в популяции 25–44 лет г. Новосибирска составила 42,4%, у мужчин – 42,7%, у женщин – 42,1%. Обнаружено, что в молодой популяции до 45 лет АО оказывает прямое влияние на развитие АГ (отношение шансов (ОШ) 2,550, 95%-й доверительный интервал (95%-й ДИ) 1,899–3,422, р = 0,0001), ХБ (ОШ = 1,830, 95%-й ДИ 1,326–2,527, р = 0,0001), гиперХСемии (ОШ = 1,486, 95%-й ДИ 1,193–1,851, р = 0,0001), гипер-ХС-ЛНПемии (ОШ = 1,527, 95%-й ДИ 1,222–1,907, р = 0,0001), обратное влияние на развитие сниженной СКФ (ОШ = 0,603, 95%-й ДИ 0,427–0,852, р = 0,004). В мужской популяции до 45 лет АО оказывает прямое влияние на развитие АГ, ХБ, гиперХСемии, гипер-ХС-ЛНПемии. В женской популяции до 45 лет АО оказывает прямое влияние на развитие СД, АГ, ХБ, гипер-ХС-ЛНПемии, и обратное – на развитие сниженной СКФ.Заключение. Таким образом, в популяции до 45 лет абдоминальное ожирение ассоциировано с развитием распространенных терапевтических заболеваний и патологических состояний.

Результаты секвенирования нового поколения у мужчин с пограничным удлинением интервала QT (пилотное исследование)

Highlights. Probably causal mutations of QT interval prolongation in genes associated with LQTS were found in men of the Siberian population.Aim. To detect and study mutations in individuals with borderline prolongation of the QT interval in Siberian males.Methods. The study was conducted on the material of the international project HAPIEE in the period from 2003 to 2005 and screening of young people aged 25–44, performed in Novosibirsk. The total sample of men was 1353 people aged 25 to 69 years. From each age subgroup (25–29, 30–34, ..., 65–69 years old) 2–3 samples with the highest QT values were selected . The study group consisted of 30 men who subsequently underwent sequencing of a panel of genes. The search for mutations was carried out in genes associated with long QT syndrome (LQTS): KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1, SCN4B, KCNJ5, ANK2, CAV3, SNTA1, AKAP9, CALM1 and CALM2. All identified single nucleotide variants were verified by direct Sanger sequencing.Results. Three rare variants in the LQTS genes have been identified: p.P197L of the KCNQ1 gene, p.R176W, and p.D1003GfsX116 of the KCNH2 gene.Conclusion. In Caucasian men from the Novosibirsk population with borderline prolongation of the QT interval, probably causal substitutions in the LQTS genes – KCNH2 and KCNQ1, contributing to the prolongation of the QT interval, were found. To clarify the spectrum and frequency of occurrence of various mutations in genes, life-threatening arrhythmias in the population, additional studies are needed on extended samples.Основные положения. У мужчин сибирской популяции обнаружены, вероятно, причинные мутации удлинения интервала QT в генах, ассоциированных с LQTS.Цель. Обнаружить и изучить мутации у мужчин сибирской популяции с пограничным удлинением интервала QT.Материалы и методы. Исследование проведено на материале международного проекта HAPIEE в период с 2003 по 2005 г. и скрининга молодых людей 25–44 лет, выполненного в Новосибирске. Общая выборка мужчин составила 1 353 человека в возрасте от 25 до 69 лет. Из каждой возрастной подгруппы (25–29, 30–34, …, 65–69 лет) выбрано по 2–3 образца с наибольшими значениями QTc. Исследуемая группа состояла из 30 мужчин, которым в дальнейшем выполнено секвенирование панели генов. Поиск мутаций проведен в генах, ассоциированных с синдромом удлиненного интервала QT (LQTS): KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1, SCN4B, KCNJ5, ANK2, CAV3, SNTA1, AKAP9, CALM1 и CALM2. Все выявленные однонуклеотидные варианты проверены методом прямого секвенирования по Сэнгеру.Результаты. Идентифицированы три редких варианта в генах LQTS: p.P197L гена KCNQ1, p.R176W и p.D1003GfsX116 гена KCNH2.Заключение. У мужчин европеоидной популяции, жителей Новосибирска, с пограничным удлинением интервала QT обнаружены вероятные причинные замены в генах LQTS – KCNH2 и KCNQ1, способствующие пролонгации интервала QT. Для уточнения спектра и частоты встречаемости различных мутаций в генах, жизнеугрожающих аритмий в популяции необходимы дополнительные исследования на расширенных выборках

ASSOCIATION OF COAGULATION FACTORS WITH THE PRESENCE OF UNSTABLE ATHEROSCLEROTIC PLAQUES IN THE CORONARY ARTERIES

Objective. This study was devoted to examinationof some factors of blood coagulation (factor II, factor VII, factor XII, antithrombin III) in order to find their associations with biomarkers of endothelial dysfunction (endothelin 1, monocyticchemoattractant protein type 1, MCP-1, lipoprotein (a), LP (a), adhesive molecules sVCAM-1, asymmetric dimethylarginin, ADMA, homocysteine), inflammation (interleukins, IL-6, IL - 8, C-reactive protein, CRP) and with unstable atherosclerotic plaques in the coronary arteries in men with coronary atherosclerosis.Material and methods. In 93 men with coronary atherosclerosis without acute coronary syndrome, blood coagulation factors concentrations (factor II, factor VII, factor XII, antithrombin III) were studied in the blood with goal to find their associations with biomarkers of endothelial dysfunction (endothelin 1, MCP-1, LP(a), adhesion molecules sVCAM-1, ADMA, homocysteine), of inflammation (IL-6, IL-8, CRP) and with the presence of unstable plaques in the coronary arteries.Results. In men with unstable atherosclerotic plaques in the coronary arteries, the blood levels of factor VII and factor XII were 1.3 and 1.3 times higher, respectively, compared to men who had stable plaques in the coronary arteries. Correlation links between the blood levels of factor II and factor XII and the presence of unstable atherosclerotic plaques in the coronary arteries (r=0.239 and r=0.250, p &lt;0.05, respectively) have been revealed, as well as between coagulation factors and blood levels of LP(a), sVCAM-1, IL-6 and CRP. Results of logistic regression analysis showed that the relative risk of present of unstable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII (OR=1.008, 95 % CI 1.000-1.017, p=0.048).Conclusion. Our results indicate that elevated blood levels of the Hageman factor may be a new biomarker of probability of unstable atherosclerotic plaques presence in the coronary arteries

Analysis of f5 gene polymorphism in men with coronary atherosclerosis using whole exome sequencing

Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the APС cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II–IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing. Material and methods. The study was conducted in the framework of the Program of joint research work IIPM — branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E.N. Meshalkin» Ministry of Health of Russian Federation. The study included 30 men aged 40–70 years with coronary angiography-­verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II–IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA). Results. In 30 patients, 29 single-­nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown. Conclusion. The single-­nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome