Aim. To perform clinical and instrumental examination and genetic testing using the method of exome sequencing of proband and his relatives of 1 and 2 degrees of kinship with myofibrillary myopathy and non-compaction cardiomyopathy.

Material and methods. The object of the study: proband with non-compaction cardiomyopathy and his relatives of 1 and 2 degrees of kinship. All participants underwent clinical and instrumental examination including: blood collection for genetic testing, complete cell blood count, biochemical blood assay (levels of total protein, alanine-aminotransferase, aspartate aminotransferase, lactate dehydrogenase, bilirubin, urea, creatinine, uric acid, potassium, sodium, creatinekinase, MB-fraction of creatinekinase, brain natriuretic peptides, C-reactive protein), coagulation profile (partial thromboplastin time, thrombin clotting time, levels of antithrombin III, INR, D-dimer), ECG, Holter ECG monitoring, cardiac MRI). The non-compaction myocardium was diagnosed according to echocardiographic criteria of non-compaction myocardium. Sequencing was performed with genomic sequenator Illumina HiSeq 1500 (Illumina, USA). Genomic libraries were prepared with Kapa Library Amplification Kit (Roche, Switzerland), NimbleGen SeqCap EZ Exome v3.0 (Roche, Switzerland) were used for exome enrichment. Then bioinformatic analysis was done; variants in 188 genes associated with any cardiomyopathy development were prioritized and assessed for pathogenenity.

Results. Proband was diagnosed with myofibrillar myopathy and familial form of non-compaction cardiomyopathy (according to MRI and echocardiographic criteria). Novel probably pathogenic variant was found in DES gene — c.330_338del. Other pathogenic and probably pathogenic variants were not found. Conclusion. Novel variant of DES gene c.330_338del is probably responsible for the development of myofibrillar myopathy and non-compaction cardiomyopathy.

Aim. Evaluation of the association of variation sites G-1082A (rs3024491) and C-592A (rs1800872) gene IL10 with one year outcomes of ST elevation acute coronary syndrome (STEACS).

Material and methods. Totally, 178 patients included, with STEACS in whom the polymorphisms C-592А (rs1800872) and G-1082А (rs3024491) of the gene IL10 were checked. Genotyping was done with TaqMan “iCycler iQ” (BIO-RAD, USA). To the control group 185 relatively healthy persons included living in Kemerovo city. In 93, the concentration of interleukin-10 (IL-10) was measured by the hard-phase immune-enzyme assay, by BIOSOURCE (Belgium). Reference values of IL-10 were set at 2,98 (1,75-4,31) pg/mL. At the one-year stage, endpoints developed in 42 (23,5%) patients, progressive angina — in 30 (16,8%); cardiovascular mortality for one year reached 1,1% (n=2), nonfatal myocardial infarction developed in 6 (3,4%), ischemic stroke — in 4 (3,2%) patients.

Results. While comparing IL-10 concentrations in STEACS with the reference values in Kemerovo city inhabitants, relatively low concentration was revealed in STEACS patients (0,38 vs 2,98 pg/mL; p=0,001). Association analysis of the variation sites of IL-10 with adverse outcomes during one year showed that genotype А/С rs3024491 (G-1082А) of gene IL10 is associated with the development of adverse outcome after NSTEACS. Endowment analysis towards the endpoint during 12 months showed that the most adverse is heterozygous carriage of А/С rs3024491 (G-1082А) gene IL10 (р=0,048).

Conclusion. In NSTEACS patients genotype С/С rs1800872 (С-592А) gene IL10 associated with lots of cardiovascular risk factors, but genotype А/А rs3024491 (G-1082А) on the contrary, shows associations with protective factors. Genotype A/C of polymorphic variant rs3024491(G-1082А) gene IL10 is associated with adverse yearly outcomes in STEACS patients.

Aim. To check the association of sudden cardiac death (SCD) with mononucleotide polymorphisms rs62116755 gene GACAT3, rs12170546 gene PARVB, rs16994849 gene PLCB1, rs78143315 gene PDCD6IP, that were set as genetic markers of SCD in previous full-genome associative original study.

Material and methods. Group of SCD (n=388, mean age 52,9±9,2 y.o., males — 77,2%, females — 22,8%) was formed by the SCD criteria of World Health Organization and European Society of Cardiology. Controls matched by sex and age (n=387, mean age 52,4±8,8 y.o., males — 62,3%, females — 37,7%) from the DNA banks of international studies MONICA, HAPIEE. Separation of DNA was done with the phenol-chlorophorm extraction. Genotyping was done by polymerase chain reaction with further polymorphism analysis of the lengths of restrictional fragments.

Results. There was no association with SCD of the mononucleotide polymorphisms rs62116755 gene GACAT3, rs78143315 gene PDCD6IP. In SCD group the number of TT carriers rs12170546 gene PARVB was significantly lower than in controls (OR =1,66, 95% CI 1,25-2,21, p=0,001; OR =0,67, 95% CI 0,50-0,90, p=0,009, respectively). In the group younger than 50 y.o. the number of GG carriers rs16994849 gene PLCB1 was significantly higher, and of genotype AA — lower, comparing to the controls (OR =4,92, 95% CI 1,01-23,20, p=0,032; OR =0,54, 95% CI 0,31-0,93, p=0,029, respectively). In males older than 50 the part of GG carriers rs16994849 gene PLCB1 was significantly lower than in control group (OR =0,11, 95% CI 0,01-0,91, p=0,024).

Aim. To assess the associations of polymorphism T-786C gene NOS3 with the severity of clinical course of coronary heart disease (CHD) and platelet aggregatability in the selection of patients receiving clopidogrel and acetylsalicylic acid (ASA) compounds after selective coronary intervention.

Material and methods. In the study, 203 CHD males included, taking ASA and clopidogrel as double antiplatelet therapy for coronary intervention. The test performed, of induced platelet aggregation with adenosine diphosphate (ADP) (2,5 mcM and 5,0 mcM) and epinephrine (0,2 mcM). Genotyping was done with the allele specific polymerase chain reaction (“SNP-express”, SPF Litekh, Russia). Statistics was done with Mann-Whitney test, Kruskal-Wallis test and Pearson chisquare or bi-test by Fisher. Differences were taken as significant at p<0,05.

Results. In the studied group, genotypes -786TT, -786TC, -786CC were found with the prevalences 72 (35,4%), 99 (48,8%), 32 (15,8%), respectively. For the carriers of -786CC there was found highest grade of platelet aggregation with ADP 2,5 mcM (p=0,047) and with epinephrine (p=0,008). Carriers of -786TC had the highest left ventricle ejection fraction (p=0,035).

Conclusion. In the selection of CHD males taking ASA and clopidogrel, carriage of -786CC polymorphism T-786C gene NOS3 was related to higher platelet aggregation in response to ADP and epinephrine. For these patients, the carriage of genotype -786CC gene NOS3 might be a predictor of thrombotic complications after coronary stenting and more adverse outcome of CHD.

Aim. To evaluate the utilization of complex significance evaluation in Russian population, of genetic markers of myocardial infarction identified in entire-genomic associative studies.

Material and methods. Group of MI patients (n=200) and control group (n=420) were created based on populational selection of 45-69 year old citizens of Novosibirsk (9400 persons), collected during the international project HAPIEE; myocardial infarction patients, admitted to intensive care unit of the Hospital № 1 (160 persons); sudden cardiac death victims, post forensic investigation (n=285). Longevity group was collected during home visits and in the nursing houses (n=85). Genomic DNA was extracted from venous blood and myocardial tissue by phenolchlorophorm method. Genes polymorphism was tested with PCR real-time according to the protocol by equipment developer (TaqMan, Applied Biosystems, USA), device ABI 7900HT. For the study, the following MNP were selected: rs499818, rs619203, rs10757278 and rs1333049 (chr. 9), rs1376251, rs2549513, rs4804611, rs17465637.

Results. Mononucleotide polymorphisms, that did not show differences at pretest stage, showed significant distinctions in the studied population. Two MNP were closely linked: rs10757278 and rs1333049 (chr. 9) so for further assessment the rs1333049 was retained. Among other seven, only five MNP showed relation with MI of various strength. Some, like the rs1333049 showed association with MI in all groups and subgroups, while the others — only in separate groups, with restriction by sex and gender. The rs2549513 and rs17465637 showed to be not associated with CHD at all, though rs2549513 showed association with lipid and glucose metabolism, as with the severity of coronary atherosclerosis and adverse prognosis for 1 year post-MI. The rs17465637 was just poorly associated with BMI.

Conclusion. Complex approach to assessment of polymorphism role is quite demanding, but provides with a high grade of insurance in the significance of the results obtained, of non-random character of the results, and makes it to choose the most credible, that have showed association not only with the main pathological phenotype, but with its risk factors.

Aim. Identification of the genes, different in the level of DNA methylation among the cells  of intact  or  atherosclerotic arteries  in patients  with coronary  and  carotid atherosclerosis.

Material and methods. Into the study group, atherosclerosis patients  were included, who had undergone coronary bypass  surgery or carotid endarterctomy, and relatively healthy individuals. The assessment of methylation level of various 27578  CpG-sites/14475  genes   was  done  with the  microchip  Infinium Human Methylation27 BeadChip (Illumina) in the specimens of atherosclerotically changed coronary (n=6), carotid (n=6), intact internal thoracal arteries (n=8) and large saphenous veins (n=8). Level of methylation in the locus 2q31.1 (HOXD4/HOXD3/MIR10B)  was  measured with bisulphite  pyrosequencing of DNA in the  vessels specimens and leucocytes  of the same  patients  (n=130), as in the leucocytes  of relatively healthy men (n=110).

Results. In the cells of atherosclerotically  changed arteries,  comparing  to intact vessels,  the change  of methylation level by 20% and more is found for 46 CpG-sites/42 genes  (pFDR <0,05).  Of those  8 genes  (TLR4,  TRAF1,  ABCB11,  NPR2, ALOX12, TMEM182, ALX4 и FABP1) are known candidates for atherosclerosis or its risk factors by the results of genetics  studies.  Most number of CpG sites, where the highest  decrease of methylation found in the cells of atherosclerotically  changed arteries  comparing  to the intact, were located  in the locus 2q31.1,  with the genes HOXD4/HOXD3/MIR10B. In leucocytes  of patients the level of methylation of one of the  CpG-sites   in  locus  2q31.1   (HOXD4/HOXD3/MIR10B)  higher  in  smokers (18±5%), than non-smokers (14±6%; p<0,05),  and level of methylation of one of CpG-sites in this area of genome is lower in those who had previous ischemic stroke (18±8%) comparing to those with no stroke anamnesis (20±7%; p<0,05).

Conclusion. Lowest part of the identifiable differently methylated genes  among the cells of lesioned  arteries  and intact vessels  is related  to atherosclerosis or its risk factors  as a result of genetic  studies  on genetic  associations. It is found that the change of methylation level in locus 2q31.1 (HOXD4/HOXD3/MIR10B) is associated with atherosclerotic lesion of arteries,  and in leucocytes  of patients  the grade  of methylation in the studied  region of genome  is related  to smoking and ischemic stroke.

Aim. To assess biochemical  and  genetic  markers  associated with the  level of oxidized low density lipoproteides (oxLDL).

Material and methods. Patients with various cardiovascular  risk according  to the SCORE scale were included in this study. Biochemical parameters were measured in blood serum  with automatic  analyzer Architect C8000 (Abbott, USA). OxLDL level was measured with the  hard-phase immune-enzyme  assay  Oxidized LDL  ELIsA (Mercodia, sweden). Genotyping was performed  via the Cardio-MetaboChip microarrays (Illumina, USA). Seventeen single-nucleotide polymorphisms (SNP) of the  APOB gene  were  included  into analysis:  rs676210,  rs1042034,  rs6728178, rs6754295,  rs673548,  rs6711016,  rs11902417, rs10184054, rs6544366, rs4564803, rs7557067, rs2678379, rs533617, rs679899, rs1801695, rs1367117, rs1042031.  The association  study between SNP and oxLDL level was performed by the ROC-analysis. Based  on results,  the group of SNP was selected. According to this group,  the  total SCORE  (TS) showing the  level of genetic  susceptibility to an increased oxLDL level was calculated.

Results. The present study included 717 patients ranging from 28 to 84 years old (with the median of 57), 204 men (28.45%). The oxLDL level varied from 21,03 to 163,72 U/dL (median 68,5) and correlated with the levels of total cholesterol  (TC), triglycerides (TG), low density cholesterol  (LDL-C), C-reactive  protein (C-RP) and apolipoprotein B-100 (ApoB-100). The highest coefficients of correlations (p<10^-10) were derived for APOB-100 and LDL-C (0,61 and 0,55, respectively). Fourteen SNPs of the APOB gene  (rs6728178,  rs11902417, rs6544366,  rs4564803,  rs6754295, rs7557067, rs1042034, rs2678379, rs676210, rs673548, rs679899, rs6711016, rs10184054, rs1042031)  were significantly associated with the oxLDL. For the ts calculation we used only ten out of fourteen SNP because of the presence of linked SNP. Patients  with ts ≤3 were referred  to as those  who had genetic  susceptibility to the increased oxLDL level due to the protective role of most sNP. The regression study has revealed that patients with the same ApoB-100 level and with ts ≤3 had higher oxLDL level in average  of 10 units than the patients with the ts>3 (p<10    ),and the patients with the same LDL-C level by 5 units, respectively (p<10  ).

Conclusion. The oxLDL level depends on the level of LDL-C and ApoB-100 in blood, as well as on the genetic susceptibility — a combination of the SNP of APOB gene.

Aim. The aim of the present study was to evaluate  the contribution of 11 singlenucleotide  polymorphisms  (SNPs) and  production  factors  to the development  of arterial  hypertension  (AH) in men  in an  organized  workers  cohort  of machinebuilding plant.

Material  and  methods. The study  included  men  aged  20-65  years  who had contact  with production  factors  (PF) during  at  least  50%  of the  working time. Genotyping of 11 SNPs was performed using TaqMan  real-time PCR. Data statistical analysis was carried out using statistica 8.0 and SAS, v. 6.12 software.

Results. 583 men were included in the study, 205 of those had AH, 378 did not. The groups differed significantly in age, presence of higher education,  the frequency of combination of two or more components of the metabolic syndrome and the severity of its individual components: weight, waist circumference, level of total cholesterol, triglycerides, low density lipoprotein cholesterol, glucose. As a result of genotyping, it was found that the frequency distribution of genotypes between groups with and without AH significantly differed  for two SNPs  — rs2932538  (p=0,0414)  in the MOV10 gene   and  rs4373814   (p=0,0344)   in  the  CACNB2 gene.   Combining information on several SNPs in the genetic  risk SCORE  (GRS) it was shown that the mean value of the total GRS in the groups  with and without AH was 0,0382±0,119 and  0,0195±0,111, correspondingly. The differences   between  the  groups  were significant (p=0,032). Based on the results of multivariate analysis, it was shown that the independent factors associated with the presence of AH in participants were age (OR=1,057 (1,037-1,076), p=0,0001), the presence of two or more components of the metabolic syndrome  (OR=2,519 (1,621-3,914), p=0,0001)  and the total GRS, consisting  of 11 SNP (OR=1,479 (1,02-2,143), p=0,04).  PF adjusting for the age were not associated with the presence of AH.

Conclusion. In men, who had direct contact with PF at machine-building plant, GRS consisting of 11 SNPs was an independent factor influencing the presence of AH. The results  show the necessity  of practical  USAge  of genetic  tests  together  with traditional risk factors  assessment with the aim for increase of AH risk estimation precision and for carrying out individual prevention.

Aim. Evaluation of the associations of allele variant of gene VЕGFR2 rs2305948 with atherosclerotic  lesion  of  coronary  arteries   in acute   coronary  syndrome  (ACS)  patients in the North (Surgut city) and big cities of the Siberian Federal District (SFD) (Novosibirsk, Irkutsk, Kemerovo).

Material  and  methods. Totally, 258  consecutive  ACS patients  investigated,  at admission  to cardiological in-patient  clinics of big cities of the North (Surgut, 78 patients) and SFD (180 patients). All patients underwent coronary arteriography and genetic test (the allele variant assessment VЕGFR2 rs2305948).

Results. In Surgut patients the allele variant VЕGFR2*CC is directly linked with the lesion  of  proximal  and  intermediate   part  of  three  main  arteries   >70%  (PTA) (χ²=4,68; p=0,031), PTA and left main stem stenosis >50% (χ²=7,02; p=0,008), and in patients from SFD VЕGFR2 *CT + *TT is directly associated with hypercholesterolemia (HC) (χ²=8,53; p=0,003). Combination of allele variant VЕGFR2*CC with HC directly influences PTA of stem stenosis >50% in ACS patients  in Surgut (Exp (B) =4,441; 95% CI (1,351; 14,601); p=0,014). Combination of allele variant VЕGFR2*CC with HC directly influences stenosis >70% existence in at least three coronary arteries, in Surgut patients (Exp (B): 3,697; 95% CI (1,304; 10,486);p=0,014), as in SFD patients exp (B): 4,460; 95% CI (1,306; 15,236); p=0,017).

Conclusion. Allele variant VЕGFR2*СС does directly influence the existence of coronary atherosclerosis of various grade severity in patients with ACS in the North, and if combined with VЕGFR2*СС and HC is also a risk factor for coronary atherosclerosis not only in the North but in SFD cities as well.

Aim. Evaluation of the association  of rs17465637 gene  MIA3 (1q41),  rs4804611 gene  ZNF627 (19p13.2),   rs2549513   (16q23.1),   rs619203   gene  ROS1  (6q22), rs1333049 (9p21.3), rs1376251 gene TAS2R50 (12p13.2) with arterial hypertension (AH), myocardial   infarction  (MI),  metabolic   syndrome   (Ms)   and   coronary atherosclerosis (CAS) in Yakutia inhabitants depending  on ethnicity and gender.

Material and methods. The results analyzed, of the assessment of the patients with verified CAS (396 males, 60 females) and persons with no clinical signs of CHD (212 males, 271 females)  age 45-64 y.o., from native and non-native Yakutia ethnicities. The period of the study: 2007-2010 years. Genomic DNA was extracted  from venous blood by phenol-chlorophorm method.  Genes  polymorphism was tested with PCR real  time  according   to  the  manual  of the  equipment   (probes   TaqMan  ,  Applied Biosystems, USA) on the device ABI 7900HT. In the study, the following mononucleotide polymorphisms  were  included  (MNP): rs17465637 gene  MIA3,  rs4804611   gene ZNF627, rs2549513  (chr. 16), rs619203  gene ROS1, rs1333049  (chr. 9), rs1376251 gene TAS2R50. For diagnosis of Ms, IDF 2005 criteria were applied.

Results. Association of AH was found in native inhabitants — males with genotype СС rs1376251  gene  TAS2R50 (p=0,004),  in females  with АА rs2549513  (chr. 16) (p=0,028)  and  rs4804611   gene   ZNF627  (p=0,033);  in non-native  inhabitants (regardless the gender and in females) — rs619203 gene ROS1 (p=0,000). Relation was found for MI in native inhabitants with genotype  ТТ rs1376251  gene  TAS2R50 (p=0,005); in non-native heterozygous males rs17465637 gene MIA3 (p=0,047) and rs619203 gene ROS1 (p=0,009), as homozygous АА rs2549513 (chr. 16) (p=0,041). The associations were found for Ms among  native inhabitants  in male carriers  of genotypes АА rs17465637 gene MIA3 (p=0,029) and heterozygous rs4804611 gene ZNF627 (p=0,034),  as  heterozygous regardless the  gender  rs2549513  (chr.  16) (p=0,016) in non-native inhabitants in male (p=0,016) and female (p=0,005) carriers of  GG rs619203   gene   ROS1  and  heterozygous  females   rs1333049   (chr.  9) (p=0,031).  With the  CAS,  the  association   found  in native  heterozygous males rs17465637 gene  MIA3 (p=0,040)  and  carriers  of ТТ rs1376251  gene  TAS2R50 (p=0,006);  in non-native  males  with CG rs619203  gene  ROS1 (p=0,020),  in nonnative females with  АА rs4804611 gene ZNF627 (p=0,008), heterozygous rs1333049 (chr. 9) (p=0,030) and rs2549513  (chr. 16) (p=0,024).

Conclusion. First time in inhabitants of Yakutia REpublic, the genome  wide results replicated,  of the association  study with AH, MI, Ms, CAS. These genetic  markers can  be  utilized for the  risk assessment of cardiovascular   diseases in Russian (Yakutia) population.

Aim. To assess the prevalences of genotypes and alleles polymorphisms of reninangiotensin-aldosterone  system,  and  β2-adrenoreceptors,  and  to  evaluate  the results  in regard   to  vasopressor  levels  in blood  serum  in essential   systemic hypertension  (ESH) with the  left ventricle hypertrophy  (LVH)  and  with none,  in Dagestan  Republic population.

Material and methods. To the assessment, 98 patients included with the diagnosis “essential systemic hypertension  with or none LVH”. Genotypes  were assessed, of polymorphism A1166C gene AGTR1 and polymorphism Arg16Gly gene ADRB2. The testing of the polymorphisms was performed  with allele-specific polymerase  chain reaction.  Level of angiotensin  (At) II, endothelin (et) 1-21 and aldosterone (AS) in blood serum was measured by the hard-phase IeA. Level of ACe was measured by enzymatic method. Statistics was done with the software statistica (version 6.0) and “Biostat 4.03”.

Results.  In EAH  patients   with LVH  the  prevalence   of  Arg/Arg polymorphism Arg16Gly gene  ADRB2  was  lower than  in control.  In EAH  with no LVH  there  is significant decline  of AC genotype  prevalences of polymorphism  A1166C gene AGTR1 and genotype  Arg/Arg polymorphism Arg16Gly gene ADRB2. Level of EТ1-21  and АТ II in the group of EAH with no LVH patients was significantly higher than in controls. Level of AT II in EAH with LVH was significantly higher than none LVH group. Increase of the levels of these mediators of AH was followed by a decline of AS level in the groups  of patients  comparing  to controls. In EAH group with LVH significant increase of et 1-21 was associated with the carriage of As polymorphism A1166C gene AGTR1, and genotypes АА and СС of the same polymorphism were associated with the decrease of levels of EТ1-21. In EAH with no LVH a significant decrease of At  II  level was found in the  carriers  of AA  and  AC genotypes of polymorphism A1166C  gene   AGTR1.  Also, the  association   was  found  of  all  genotypes  of polymorphism Arg16Gly gene ADRB2  with the decrease of АТ II.

Aim. To assess the prevalence  of polymorphism of the gene  AGT and its relation with systemic  hypertension  risk in the  ethnicities  of Gornaya  Shoria (Mountain Shoria).

Material and methods. A clinical-epidemiological study conducted, of compactly inhabiting people of uneasily reachable areas of Gornaya Shoria (settlements Orton, Ust-Kabyrza) and city-like settlement Sheregesh. Based  on the name  lists, 1178 inhabitants included from the settlements. In 398 persons, blood was collected from cubital vein, fasting, in the morning for genotyping. Extraction of DNA from the blood was done with phenol-chloroform  method.  Polymorphism of AGT (М235Т, rs699) gene was tested with PCR.

Results. In general,  in both  ethnicities,  the  prevalence  of AGT  did not  differ significantly. However, among  men there was national specifics found for the C/C genotype:  in the Shortsy group  its prevalence  (27,8%) was higher comparing  to non-native inhabitants (10,3%). In shortsy male cohort the carriers of T/C had odds ratio for glucose metabolism and arterial hypertension at 2,45 and 2,21, respectively; in females with C/C carriage  the risk of dyslipidemia was 3,37. Among females of non-native  nationality  there   were  associations  found  for  T/T  genotype   with hypercholesterolemia. The odds  ratio for higher cholesterol  among  homozygotes T-allele was 4,3 times higher comparing to T/C and C/C.

Conclusion. Regardless the absence of differences  in genotypes prevalences of AGT, there were differences  revealed  of the association  of risk factors  of arterial hypertension   according   to  ethnicity.  In shortsy  cohort  the  C/C  genotype   was associated with hyperbetacholesterolemia and dyslipidemia, and genotype  T/C — with glucose  metabolism.  In non-native cohort T/T genotype  was associated with dyslipidemia.

Danon disease (DD) is a rare and complex pathology, difficult for diagnostics, with multisystemic presentation, which demands for multidisciplinary clinical approach, incl. cardiologists,  genetics, neurologists,  ophthalmologists  and rehabilitologists. The disorder is characterized by a classical triad of signs: phenotype  of hypertrophic  cardiomyopathy  (HCMP), skeletal myopathy and intellect deficit of various grade.

The prevalence of DD until recently is not known precisely. It is due to unrecognized origin of  myocardial  hypertrophy  caused  by  lysosomal  glycogen  retention  in cardiomyocytes. DD is a phenocopy of HCMP, but differs by a malignant course and adverse  outcome.  Rapid progression of the disease (with the development  of heart failure) is known even in moderate myocardial hypertrophy,  that requires  frequent dynamic follow-up and on-time  evaluation of heart  transplantation. Is myocardial fibrosis is found in DD, it is prognostically  adverse  factor for arrhythmia risk and sudden cardiac death. Such patients should be regarded as potential candidates for cardioverter-defibrillator implantation for primary SCD prevention.

The article  presents with clinical CASe  of delayed  diagnostics  of DD related  to mutation  in the  gene  for lisosome-associated membrane protein  2 (LAMP2), in details clinical signs are provided, as differential diagnostics  methods.

Friedreich’s ataxia (FA) is one of the most prevalent variants of the inherited ataxias. The disease is characterized by complicated phenotype that includes neurological signs (ataxia, sensory polyneuropathy, dysarthria, disorders of deep sensitivity, areflexia, pyramid symptoms with lower extremities involvement, vegetative disorders, sometimes — psychopathological symptoms), cardiological disorders (cardiomyopathy, heart failure, arrhythmias), and disorders of carbohydrate metabolism, and skeletal deformities. If neurological disorders lead to significant decrease of life quality and disability, cardiovascular complications are the main cause of fatal outcome in FA. It is worthy to mention that involvement of the heart into pathological process might long remain undiagnosed.

Recently, most of abroad and local publications on FA are related to neurological presentation. Cardiovascular side of the problem in the scientific society remains underestimated, regardless the risk of sudden death and of heart failure (due to symmetric myocardial hypertrophy with the areas of intramyocardial fibrosis) being high.

We present clinical and genetic observation of a 27-year old patient with FA, moderate neurological disorders and severe myocardial hypertrophy. The article is focused on the contemporary clinical and diagnostic aspects of FA associated cardiomyopathy.

Aim. Apolipoprotein E (apoE) and paraoxonase 1 (PON1) participate in regulation of blood lipoprotein levels, as well as in their hydrolysis and oxidation. We assumed that individual alleles of the apoE and PON1 genes, along with the changes in concentrations of these substances, contribute to the development of calcific aortic valve stenosis (CAVS).

Material and methods. The study group included 108 patients with CAVS and 46 patients without any signs of the aortic valve lesions were determined. The serum apoE and PON1 levels were measured by ELISA, the Leu28Pro mutation in the apoE (rs429358) gene and the Gln192Arg mutation in the PON1 (rs662) gene were detected using PCR SNP-EXPRESS electrophoresis detection scheme.

Results. Increased serum levels of apoE (0,05 vs 0,03 µg/l, p<0,001) and PON1 (4,8 vs 3,4 µg/ml, p<0,05) were detected in CAVS patients. The frequencies of allelic polymorphisms of the apoE and PON1 genes were similar in the two groups. 28Pro allele of the apoE gene was associated with increased level of low density lipoproteins in CAVS (3,9±1,05 vs 3,13±1,08 mmol/l, p<0,02) and total cholesterol in the controls (6,2; 6,5 vs 5,11±0,89 mmol/l, p<0,05). The PON1 genotype had no effect on lipid metabolism in CAVS patients. Controls with 192Gln allele demonstrated decreased blood levels of apoE (0,02 vs 0,05 µg/l, р<0,01) and increased PON1 serum concentration (4,1 vs 3,3 µg/ml, р<0,01).

Conclusions. CAVS patients have increased serum levels of apoE and PON1; the apoE level is an independent predictor of aortic calcification. Polymorphic markers Gln192Arg of the PON1 gene and Leu28Pro of the apoE gene are not associated with CAVS.

Aim. To assess the association of efficacy and safety endpoints with simultaneous carriage of polymorphic variants of the gene CYP2C19: rs4244285 (*2), and rs12248560 (*17) in treatment with clopidogrel.

Material and methods. In the study, 289 patients included, from large cities of Siberia, underwent coronary stenting for acute coronary syndrome. All participants were assessed for alleles CYP2C19*2, *3, *17, and clinical outcomes were followed for 30 days (thrombotic complications, bleedings).

Results. It was found that simultaneous carriage of CYP2C19*2 and CYP2C19*17 alleles is associated with the risk of serious adverse events development of thrombotic origin comparing to the absence of such polymorphism carriage (p=0,016), and with general adverse events risk related to insufficiency of clopidogrel action (р=0,046).

Conclusion. According to the study results, subjects with the *2/*17 carriage should be classified to a delayed clopidogrel metabolism group, as in the group definite and probable stent thrombosis were found significantly more prevalent.

The article is focused on the review of recent epidemiological and clinical data on the prevalence of systemic hypertension and its influence on the outcomes of cardiovascular diseases. An efficacy is argued, as the adherence for and safety of antihypertension therapy by combinational drug “single-pill” Triplixam® (“Les Laboratoires Servier”, France), containing perindopril/indapamide/amlodipine. The usage of the medication is grounded, aiming against target organ damage and development of cardiovascular outcomes.

Atrial fibrillation (AF) is a significant risk factor for stroke and systemic embolism. For prevention of these complications, most AF patients are indicated to take anticoagulants, that reduce the risk cardioembolic strokes, but increase the risk of bleedings, and the most prevalent are gastrointestinal (GIB).

Aim. To assess the rate of pathological changes in esophagus, stomach and duodenum, predisposing for GID, in AF patient with higher risk of stroke and absolute indications for anticoagulation therapy.

Material and methods. The analysis done, of case histories of hospitalized patients in the therapeutical university clinics, in the year 2016; of those — 263 with non-valvular AF. Among 222 patients with AF and higher risk of stroke, who had indications for anticoagulants, 103 underwent screening fibroesophagogastroduodenoscopy (FEGDS).

Results. The FEGDS, performed in 103 patients with non-valvular AF and high risk of stroke, in 45,6% revealed diseases predisposing to GIB, including esophageal cancer — 1 (2,1%), gastric ulcer — 4 (8,5%), duodenal ulcer — 2 (4,3%), erosive esophagitis and reflux disease — 5 (10,6%), varicose veins of esophagus — 4 (8,5%), erosive gastritis — 31 (66,0%) and erosive duodenitis — 3 (6,4%). Combination of diseases was found in 10 (21,3%) patients.

Conclusion. Patients with non-valvular AF and high stroke risk, before starting therapy with anticoagulants, it is aimworthy to perform FEGDS for on-time screening for esophageal, gastric, duodenal pathologies predisposing to GIB.

The lecture is focused on the exploration of genetic and physiological mechanisms of essential systemic hypertension (ESH). A very brief historic review is provided on the first clinical meanings of the ESH. Then some speculation provided, on its etiology, evolutionary-genetic roots regarding the formation of the main BP regulation systems. More detailed, the data is shown on genetic base of hypertensive conditions and ESH. Also, some discussion given on the monogenic forms of arterial hypertension and polygenic fundamentals of ESH, which is the most among hypertension conditions of human. Modern methods considered for genetic origins of ESH evaluation, and a necessity is underlined for the main etiological factors revealing — as of their interrelation for development of rational treatment and prevention methods against ESH.

The review is focused on current views on the structural variation of genome of somatic cells as components related to atherosclerosis. The original data presented on the variation spectrum of DNA areas copies in peripheral blood leucocytes and arterial cells in human atherosclerosis. The future directions sketched for the research on somatic cells genome variation with the aim for pathogenetics of multifactorial diseases.