ASSOCIATION OF TREM-1 GENE POLYMORPHISMS WITH INFECTIVE ENDOCARDITIS

Infective endocarditis (IE) is a septic inflammation of endocardium, which generally involves the lining of the heart chambers and heart valves. The development of IE depends in many respects on how properly and efficiently the immune system responds to the occurrence of an infection. Innate immunity, which carries out the response to a transient bacteremia, is genetically determined in a large extent. Pattern recognition receptors, which identify pathogenand danger-associated molecular patterns, are the main effectors of innate immune response; one of these receptors is triggering receptor expressed on myeloid cells-1 (TREM-1). We hypothesized that inherited variation in TREM-1 gene may affect individual susceptibility to IE. The distribution of genotypes and alleles of rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535, and rs2234237 gene polymorphisms was investigated in 110 Caucasian (Russian) subjects with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors. Odds ratios with 95% confidence intervals were calculated. We found that rs1817537 polymorphism was associated with decreased IE risk (OR = 0.60; 95%CI = 0.37–0.99; р = 0.046, dominant model); however, this was not significant after an adjustment for multiple comparisons. Therefore, we observed no statistically significant association between the investigated polymorphisms within TREM-1 gene and IE. Further in-depth investigations in this field are necessary to shed the light on the impact of inherited variation within innate immune response genes on the development of IE

Association of polymorphisms the trigger receptor gene expressed by myeloid cells (<i>TREM-1</i>) in sporadic congenital heart defects without chromosome anomalies

Eight polymorphic loci in the TREM-1 gene (rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535 and rs2234237) were genotyped in 131 children with congenital heart defects (CHD) without proven chromosomal anomalies, and 103 conditionally healthy children (control group) matched for age and gender. Genotyping was performed by polymerase chain reaction (PCR) using TaqMan probes. The frequency of these genotypes was checked for Hardy–Weinberg equilibrium using a free tool (http://bioinfo.iconcologia.net/SNPstats). Analysis of inter-locus interactions was performed by Multifactor Dimensionality Reduction method. It was shown that the combination of four loci, i.e., rs1817537, rs3804277, rs2234246 and rs7768162 may determine susceptibility and persistence for CHD without chromosomal diseases. Increased CHD risk is associated with two-locus model rs1817537*G/G – rs3804277*T/T (OR = 8.26) and three-locus model rs2234246*C/T – rs1817537*C/G – rs7768162*A/G (OR = 13.76). The two-locus model rs1817537*С/С – rs3804277*T/T (OR = 0.03) and three-locus model rs2234246*T/T – rs1817537*C/C – rs7768162*G/G (OR = 0.03) were associated with a decreased risk for CHD without detectable chromosomal anomalies

BUILDING A TOMOGRAPHIC VELOCITY MODEL FOR SAMOYLOV ISLAND AREA (LENA DELTA) FROM LOCAL SEISMOLOGICAL DATA FOR THE PERIOD OF 2019–2021

In our paper we present the results of seismotomographic inversion for the local seismological monitoring data obtained in the area of the Samoylov Island (Lena River delta) in 2019–2021. Tomographic velocity model was used for refining hypocenter locations of local earthquakes and for geological interpretation. The results are shown as maps of anomalies of seismic waves and Vp /Vs ratios for the 5 and 10 km depths. The velocity anomalies structure made it possible to interpret low Vp /Vs ratio as rocks related to the Siberian platform, and to compare between the boundary of the low Vp /Vs area and the trace of the known geological fault running along the Olenekskaya Channel

Comparative evaluation of the expression of enzymes of the ceramide <i>de novo</i> synthesis pathway in cardiac adipose tissue and blood vessels of cardiovascular patients

Aim. To compare the expression of enzymes of the ceramide de novo synthesis pathway in cardiac adipose tissue (AT) and blood vessels of patients with coronary artery disease (CAD) and acquired heart defects.Material and methods. The study included 20 patients with CAD and 18 patients with aortic stenosis/regurgitation. Biopsies of subcutaneous, epicardial, perivascular AT (SCAT, EAT, PVAT, respectively) were obtained during surgery. Quantitative PCR test was used to evaluate the gene expression of de novo ceramide synthesis enzymes (serine palmitoyltransferase C1 and C2: SPTLC1, SPTLC2; ceramide synthase 1-6: CERS1-6; dihydroceramide desaturase: DEGS1). Statistical analysis was performed using GraphPad Prism 8 (GraphPad Software).Results. Patients with CAD were characterized by a higher level of mRNA SPTLC1 in SCAT and EAT, SPTLC2, CERS1, producing C18 ceramides, CERS5 and CERS6, generating C14-C16 ceramides in EAT, CERS2 — in SCAT, producing long-chain ceramides C20-C24, CERS4, synthesizing very long-chain ceamides C18-C20. In PVAT, a high expression of CERS4 and CERS3, which synthesizes very long-chain ceramides C26 and higher, was revealed. DEGS1 expression was highest in SCAT and EAT. In patients with heart defects, there was a high expression of CERS3 in PVAT, CERS4 in EAT and PVAT, DEGS1 in EAT. The mRNA level of SPTLC1 in SCAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and 5 in EAT, DEGS1 in SCAT and EAT among patients with CAD was higher than in the comparison group.Conclusion. Regional fat depots of the heart differed in the level of expression of enzymes of the ceramide de novo synthesis pathway. The results obtained indicate the activation of ceramide synthesis along this pathway in predominantly epicardial adipocytes in coronary pathology, which may contribute to the accumulation of long-chain ceramides in the AT of this localization

ПОСТРОЕНИЕ СЕЙСМОТОМОГРАФИЧЕСКОЙ МОДЕЛИ РАЙОНА НАУЧНО-ИССЛЕДОВАТЕЛЬСКОЙ СТАНЦИИ «ОСТРОВ САМОЙЛОВСКИЙ» ПО ДАННЫМ ЛОКАЛЬНОГО СЕЙСМОЛОГИЧЕСКОГО МОНИТОРИНГА ЗА 2019–2021 гг.

In our paper we present the results of seismotomographic inversion for the local seismological monitoring data obtained in the area of the Samoylov Island (Lena River delta) in 2019–2021. Tomographic velocity model was used for refining hypocenter locations of local earthquakes and for geological interpretation. The results are shown as maps of anomalies of seismic waves and Vp /Vs ratios for the 5 and 10 km depths. The velocity anomalies structure made it possible to interpret low Vp /Vs ratio as rocks related to the Siberian platform, and to compare between the boundary of the low Vp /Vs area and the trace of the known geological fault running along the Olenekskaya Channel. В работе приведены результаты сейсмотомографической инверсии по данным локального сейсмологического мониторинга, полученным в районе научно-исследовательской станции «Остров Самойловский» (дельта р. Лены) в 2019–2021 гг. Полученная сейсмотомографическая модель была использована для уточнения гипоцентров локальных землетрясений и геологической интерпретации. Результаты приведены в виде скоростных аномалий P- и S-волн, а также их соотношения Vp /Vs , для глубин 5 и 10 км. Анализ структуры скоростных аномалий позволил интерпретировать зону пониженного соотношения Vp /Vs как слой пород, относящийся к Сибирской платформе, а также сопоставить границу области пониженного Vp /Vs с известным геологическим разломом, проходящим вдоль Оленёкской протоки.

EVALUATION OF THE CALCIUM-PHOSPHOR HOMEOSTASIS AND PROINFLAMMATORY STATUS OF RECIPIENTS WITH CALCIUM DEGENERATION OF CARDIAC VALVES PROSTHESES

Aim. To study calcium-phosphor homeostasis and proinflammatory status of the cardiac valves bioprostheses (BP) recipients related to their interference with calcium degeneration of biomaterials.Material and methods. A retrospective assessment was performed of the calcium-phosphor metabolism and markers of non-specific inflammatory response in recipients of BP in mitral position: with histologically confirmed calcification — group I (n=22) and with normal morphology and prosthesis function — group II (n=48).Results. In patients with BP degeneration, comparing to the recipients of biological prostheses with normal function at the background of moderate hypovitaminosis D (34,0 [21,0; 49,4] versus 40 [27,2; 54,0] pmol/L, р&gt;0,05), osteoprotegerine deficiency (82,5 [44,2; 115,4] versus 113,5 [65,7; 191,3] pg/ml, р&gt;0,05) and osteopontine (4,5 [3,3; 7,7] versus 5,2 [4,1; 7,2] ng/ml, р&gt;0,05) there was statistically significant decrease of the bone isoenzyme of alkaline phosphatase (17,1 [12,2; 21,4] versus 22,3 [15,5; 30,5] E/L, р=0,01), and significant decrease of IL-8 (9,74 [9,19; 10,09] pg/ml versus 13,17 [9,72; 23,1] pg/ml, р=0,045) with general increase of proinflammatory serum markers activity.Conclusion. Into the group of probable predictors determining the tempos of BP calcification, the following could be included: specifics of recipient metabolic status defined by the activity of bone resorption processes, and local and systemic inflammation

Associations of Cardiovascular Risk Factors and Genetic Markers with Development of Arterial Hypertension in the Population of Mountain Shoriya

Aim. To study the combined effect of cardiovascular risk factors and genetic markers that encode the proteins of the main components of neurophysiological systems (renin-angiotensin-aldosterone, sympathetic-adrenal systems, endothelial dysfunction) on the development of arterial hypertension among the indigenous and non-indigenous population of Mountain Shoriya.Material and methods. We performed a clinical and  epidemiological study  of the compactly settled population in the remote areas  of Mountain Shoriya. This region of middle mountains is situated in the south of Western Siberia. We examined 1409 subjects (901 subjects – the representatives of indigenous nationality [the Shors], 508 subjects – representatives of non-indigenous nationality [90% among them  were the representatives of the European ethnicity]). Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and  instrumental investigation. Polymorphisms of genes  ACE (I/D, rs 4340), АGT (c.803T&gt;C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A&gt;G, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677С&gt;Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.Results. Cardiovascular risk factors  associated with hypertension in cohort  of Shorians: hypercholesterolemia [Odds Ratio (OR) 1.54,  low density lipoproteinemia (OR 1.48), violation of carbohydrate metabolism (OR 1.53), obesity (OR 2.25), including its abdominal type (OR 1.53), the family anamnesis of early cardiovascular diseases (OR 1.88)]  and  rs4340 polymorphisms of the  ACE gene  (OR 4.39), rs5186 of the  AGTR1 gene  (OR 10.02); in the cohort of the non-indigenous ethnos – hypercholesterolemia (OR 1.87), hypertriglyceridemia (OR 1.87), obesity (OR 2.75), abdominal obesity (OR 2.73), family anamnesis of early cardiovascular diseases (OR 2.48), the polymorphism rs5186 of the AGTR1 gene (OR 26.77). Genotype G/G ADRB1 gene was characterized by protective effect against hypertension in the Shorians.Conclusion. Evaluation of the complex influence of clinical and genetic factors  on the development of hypertension in the population of Mountain Shoriya showed their comparable importance among the indigenous population and  the predominance of non-genetic factors  among the non-indigenous population

POLYMORPHISMS WITHIN INNATE IMMUNE RESPONSE, CALCIUM METABOLISM AND LIPID METABOLISM ARE PREDICTORS OF INFECTIVE ENDOCARDITIS

Infective endocarditis (IE) is a septic inflammation of the endocardium generally caused by bacteria. Despite certain advances in treatment, case fatality rate and mortality of IE are still relatively high, particularly in high-risk groups. This requires the development of novel efficient preventive approaches; one of them is a personalized medicine. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. We hypothesized that inherited genomic variation in the abovementioned pathways may determine individual susceptibility to IE. Having recruited 124 patients with IE and 300 age-, sex-, and ethnicity-matched healthy controls, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in pathways mentioned above, with the further genetic association analysis. Genotyping was performed using TaqMan allelic discrimination assay while statistical analysis was carried out utilizing SNPStats, a web tool for genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene are associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene is associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively, suggesting their possible importance for IE development. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. However, further molecular epidemiology studies are needed to thoroughly uncover the genetic basis of IE

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE