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​Russian Journal Of Cardiology, 2017, 10 (150)

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Russ J Cardiol 2017, 10 (150): 7

CLINICAL MEDICINE NEWS

Clinical medicine updates: a review of international news

Russ J Cardiol 2017, 10 (150): 8

ORIGINAL ARTICLES

DES GENE MUTATION IN A FAMILY OF PROBAND WITH MYOFIBRILLARY MYOPATHY

AND NON-COMPACTION CARDIOMYOPATHY, RESULTED IN CARDIAC TRANSPLANTATION

Myasnikov R.P.1, Shcherbakova N.V.1, Kulikova О.V.1, Meshkov А.N.1, Kharlap M. S.1, Kiseleva А.V.1, Zharikova А.А.1, Dadali Е. L.5, Semenova N. А.5, Koretsky S. N.1, Blagova О. V.4, Mershina Е. А.2, Sinitsyn V. Е.2, Drapkina О. М.1, Boytsov S. А.3

Abstract

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.

Russ J Cardiol 2017, 10 (150): 9–16

dx.doi.org/10.15829/1560-4071-2017-10-9-16

Key words: DES, exome sequencing, left ventricular non-compaction cardiomyopathy, cardiomyopathy, myofibrillar myopathy, cardiac transplantation, skeletal myopathy, heart failure, sudden cardiac death.

1National Research Center for Preventive Medicine of the Ministry of Health, Moscow; 2Treatment and Rehabilitation Center of the Ministry of Health, Moscow; 3National Medical Research Center of Cardiology of the Ministry of Health, Moscow; 4I.M. Sechenov First Moscow State Medical University of the Ministry of Health, Moscow; 5Medical and Genetic Scientific Center, Moscow, Russia.

ROLE OF THE VARIABLE SITES G-1082A AND C-592A OF GENE IL10 IN DEVELOPMENT OF ONE YEAR

ADVERSE OUTCOMES OF ST ELEVATION ACUTE CORONARY SYNDROME

Berns S. А.1,2, Shmidt Е. А.1, Makeeva О. А.1,3, Goncharova I. А.1,3, Salakhov R. R.1, Nagirniak О. А.1, Barbarash О. L.1

Abstract

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 conentration 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.

Russ J Cardiol 2017, 10 (150): 17–22

dx.doi.org/10.15829/1560-4071-2017-10-17-22

Key words: G-1082A (rs3024491) and C-592A (rs1800872) gene IL10, adverse outcome, ST elevation acute coronary syndrome.

1Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry (MSUMD), Moscow; 3SRI of Medical Genetics, Tomsk National Research Center of RAS, Tomsk, Russia.

ASSOCIATION OF THE MONONUCLEOTIDE POLYMORPHISMS RS62116755 OF GENE GACAT3, RS12170546 OF GENE PARVB, RS16994849 OF GENE PLCB1, RS78143315 OF GENE PDCD6IP WITH SUDDEN CARDIAC DEATH

Ivanova А. А.1, Maksimov V. N.1,2, Malyutina S . К.1,2, Novoselov V. P.2,3, Savchenko S. V.2,3, Voevoda М. I.1

Abstract

Aim. To check the association of sudden cardiac death (SCD) with mononucleotide polymorphisms rs62116755 gene GACAT 3, 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 GACAT 3, 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).

Conclusion. Mononucleotide polymorphisms rs62116755 gene GACAT 3, rs78143315 gene PDCD6IP were not related to SCD. Genotype ТТ of polymorphism rs12170546 gene PARVB is a genotype of risk of SCD, and genotype TC is protective. Genotype GG of polymorphism rs16994849 gene PLCB1 is the genotype of risk for SCD for those younger than 50 y. o. and is protective in those older than 50. Genotype AA of polymorphism rs16994849 gene PLCB1 is protective against SCD in those younger 50 y. o.

Russ J Cardiol 2017, 10 (150): 23–28

dx.doi.org/10.15829/1560-4071-2017-10-23-28

Key words: sudden cardiac death, GWAS, GACAT 3, PARVB, PLCB1, PDCD6IP.

1SRI of Therapy and Prevention Medicine — branch of FSBSI Federal Research Center Institute of Cytology and Genetics of SD RAS, Novosibirsk; 2Novosibirsk State Medical University, Novosibirsk; 3Novosibirsk Oblast Clinical Bureau of Forensic Expertise, Novosibirsk, Russia.

GENOTYPE -786CC OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE NOS3 AS A FACTOR OF ADVERSE CORONARY HEART DISEASE COURSE AND INCREASED ON-TREATMENT PLATELET AGGREGATION

Muslimova E. F., Rebrova T. Yu., Afanasiev S. A., Sergienko T. N., Repin A. N.

Abstract

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 chi-square 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.

Russ J Cardiol 2017, 10 (150): 29–32

dx.doi.org/10.15829/1560-4071-2017-10-29-32

Key words: polymorphism, NOS3, CHD, platelet aggregation.

SRI of Cardiology, Tomsk National Research Medical center of RAS, Tomsk, Russia.

COMPLEX EVALUATION OF THE SIGNIFICANCE OF POPULATIONAL GENETIC MARKERS ASSOCIATED

WITH MYOCARDIAL INFARCTION AND RISK FACTORS

Maksimov V.N.1, Orlov P.S .1, Ivanova А. А.1, Lozhkina N. G.2, Kuimov А. D.2, Savchenko S. V.2, Novoselov V. P.2, Voevoda М. I.1, Malyutina S. К.1

Abstract

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.

Russ J Cardiol 2017, 10 (150): 33–41

dx.doi.org/10.15829/1560-4071-2017-10-33-41

Key words: myocardial infarction, mononucleotide polymorphism, rs499818, rs619203, rs10757278, rs1333049, rs1376251, rs2549513, rs4804611, rs17465637.

1SRI of Therapy and Prevention Medicine — branch of FSBSI Federal Research Center Institute of Cytology and Genetics of SD RAS, Novosibirsk; 2FSBEI HE Novosibirsk State Medical University, Novosibirsk, Russia.

IDENTIFICATION OF DIFFERENTLY METYLATED GENES POTENTIALLY RELATED TO HUMAN ATHEROSCLEROSIS

Nazarenko M. S.1,2,3, Markov А. V.1, Koroleva Yu. А.1, Sleptsov А. А.1, Kazantsev А. N.2, Barbarash О. L.2, Puzyrev V. P.1,3

Abstract

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 CpGsites/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.

Russ J Cardiol 2017, 10 (150): 42–48

dx.doi.org/10.15829/1560-4071-2017-10-42-48

Key words: atherosclerosis, DNA methylation, microRNA, microchips, biomarkers.

1SRI of Medical Genetics, Tomsk National Research Center of RAS, Tomsk; 2SRI of Complex Issues of Cardiovascular Diseases, Tomsk; 3Siberian State Medical University (SSMU), Tomsk, Russia.

LIPID PROFILE AND GENETIC MARKERS ASSOCIATED WITH THE LEVEL OF OXIDIZED LOW DENSITY

LIPOPROTEIDES

Khlebus E.Yu.1,2, Meshkov А.N.1, Lankin V.Z.3, Orlovsky А.А.4, Kiseleva А.V.1, Shcherbakova N.V.1, Zharikova А.А.1, Ershova А.I.1, Tikhaze А. К.3, Yarovaya Е. B.4, Chazova I. Е .3, Boytsov S. А.3

Abstract

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<10-10), and the patients with the same LDL-C level by 5 units, respectively (p<10-6).

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.

Russ J Cardiol 2017, 10 (150): 49–54

dx.doi.org/10.15829/1560-4071-2017-10-49-54

Key words: oxidized low density lipoprotein, LDL-C, ApoB-100, single-nucleotide polymorphism, atherosclerosis, malondialdehyde, APOB.

1National Research Center for Preventive Medicine of the Ministry of Health, Moscow; 2Moscow Institute of Physics and Technology (State University), Moscow; 3National Canter Research of Cardiology of the Ministry of Health, Moscow; 4M. V. Lomonosov Moscow State University, Moscow, Russia.

CONTRIBUTION OF GENETIC MARKERS AND PRODUCTION FACTORS IN THE DEVELOPMENT OF ARTERIAL HYPERTENSION IN MEN IN AN ORGANIZED WORKERS COHORT OF MACHINE-BUILDING PLANT

Kiseleva A.V.1, Klimushina М.V.1, Tyupaeva S. А.2, Eliseeva N. А.1, Smetnev S. А.1, Deev А. D.1, Britov А. N.1, Meshkov А. N.1, Drapkina О. М.1

Abstract

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.

Russ J Cardiol 2017, 10 (150): 55–60

dx.doi.org/10.15829/1560-4071-2017-10-55-60

Key words: arterial hypertension, single nucleotide polymorphisms, production factors, genetic risk score.

1National Research Center for Preventive Medicine of the Ministry of Health, Moscow; 2Medical and Sanitary Institution № 170, FMBA, Koroljov, Moscow Region, Russia.

REGIONAL ASPECTS OF THE GENE POLYMORPHISM VEGFR2 WITH CORONARY ATHEROSCLEROSIS

IN ACUTE CORONARY SYNDROME

Nikolaev K. Yu.1,2, Urvantseva I. А.3, Batueva К. Yu.3, Apartsin К. А.4,5, Gorokhova А. V.5, Ganyukov V. I.6, Kochergin N. А.6, Zelenskaya Е . M.7, Lifshits G. I.7,2

Abstract

Aim. Evaluation of the associations of allele variant of gene VEGFR2 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 VEGFR2 rs2305948).

Results. In Surgut patients the allele variant VEGFR2*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 VEGFR2 *CT + *TT is directly associated with hypercholesterolemia (HC) (χ2=8,53; p=0,003). Combination of allele variant VEGFR2*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 VEGFR2*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 VEGFR2*СС does directly influence the existence of coronary atherosclerosis of various grade severity in patients with ACS in the North, and if combined with VEGFR2*СС and HC is also a risk factor for coronary atherosclerosis not only in the North but in SFD cities as well.

Russ J Cardiol 2017, 10 (150): 61–65

dx.doi.org/10.15829/1560-4071-2017-10-61-65

Key words: acute coronary syndrome, coronary atherosclerosis, allele variants of VEGFR2, hypercholesterolemia, the North.

1SRI of Therapy and Prevention Medicine — branch of SD RAS, Novosibirsk; 2Novosibirsk State University, Novosibirsk; 3Surgut State University, Surgut; 4Irkutsk Scientific Center of SD RAS, Irkutsk; 5Irkutskaya Oblast Clinical Hospital of the “Sign of Honour” Award, Irkutsk; 6Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo; 7Institute of Chemical Biology and Fundamental Medicine of SD RAS, Novosibirsk, Russia.

GENETIC MARKERS OF METABOLIC SYNDROME AND CORONARY ATHEROSCLEROSIS IN YAKUTIA

INHABITANTS

Romanova А. N.1, Voevoda М. I.2, Maksimov V. N.2

Abstract

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 TAS 2R50 (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 TAS 2R50. For diagnosis of MS, IDF 2005 criteria were applied.

Results. Association of AH was found in native inhabitants — males with genotype СС rs1376251 gene TAS 2R50 (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 TAS 2R50 (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 TAS 2R50 (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.

Russ J Cardiol 2017, 10 (150): 66–75

dx.doi.org/10.15829/1560-4071-2017-10-66-75

Key words: arterial hypertension, myocardial infarction, metabolic syndrome, coronary atherosclerosis, mono nucleotide polymorphisms, gender and ethnical specifics, Yakutia.

1Yakutsky Scientific Center of Complex Medical Problems, Yakutsk; 2SRI of Therapy and Prevention Medicine, Novosibirsk, Russia.

ANALYSIS OF POLYMORPHISMS OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND RELATION TO VASOPRESSORS IN ESSENTIAL SYSTEMIC HYPERTENSION WITH THE LEFT VENTRICLE HYPERTROPHY IN DAGESTAN REPUBLIC

Saidov M. Z., Mammaev S. N., Abdullaev A. A., Arapkhanova T . B., Israilova G. R.

Abstract

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.

Conclusion. In Dagestan population, in EAH with and with no LVH, most significant are genotypes AA, AC and CC of polymorphism A1166C gene AGTR1, and genotypes Arg/Arg, Arg/Gly, Gly/Gly and alleles Arg and Gly polymorphism Arg16Gly

gene ADRB2. Pathogenic significance of the mentioned polymorphisms is emphasized by the presence of polymorphism ET1-12, АТ II, АS in blood serum.

Russ J Cardiol 2017, 10 (150): 76–84

dx.doi.org/10.15829/1560-4071-2017-10-76-84

Key words: essential arterial hypertension, left ventricle hypertrophy, genes polymorphisms, genotypes, vasopressors, Dagestan population.

Dagestan State Medical University, SRI of Ecological Medicine, Makhachkala, Russia.

ASSOCIATIONS OF THE ANGIOTENSIN GENE POLYMORPHISM (AGT, rs699) WITH SYSTEMIC HYPERTENSION AND ITS RISK FACTORS IN GORNAYA SHORIA INHABITANTS

Mulerova Т. А.1,2, Ponasenko А. V.1, Tsepokina А. V.1, Kuzmina А. А.1, Ogarkov М. Yu.1,2

Abstract

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 Shoriya).

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.

Russ J Cardiol 2017, 10 (150): 85–92

dx.doi.org/10.15829/1560-4071-2017-10-85-92

Key words: ethnicity, gene AGT polymorphism, arterial hypertension.

1Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo; 2NSIPI — branch of Russian Medical Academy of Continuous Professional Education of the Ministry of Health, Novokuznetsk, Russia.

DANON DISEASE: A RARE SYSTEMIC DISORDER WITH THE LAMP2-CARDIOMYOPATHY

Vaykhanskaya T. G.1, Sivitskaya L. N.2, Danilenko N. G.2, Sidorenko I. V.1, Davydenko О. G.2

Abstract

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.

Russ J Cardiol 2017, 10 (150): 93–99

dx.doi.org/10.15829/1560-4071-2017-10-93-99

Key words: Danon disease, LAMP2, hypertrophic cardiomyopathy.

1Republic Scientific-Practitioner Center “Cardiology”, Minsk; 2Institute of Genetics and Cytology of NAS Belorussia, Minsk, Belorussia.

CARDIOMYOPATHY IN THE FRIEDREICH ATAXIA: CLINICAL PRESENTATION AND DIAGNOSTICS

OF COMPLICATIONS

Fomicheva Е. I.1, Myasnikov R. P.1, Selivyorstov Yu. А.2, Dadali Е . L.3, Kotalevskaya Yu. Yu.4, Kharlap М. S.1, Koretsky S. N.1, Nuzhny Е. P.2, Mershina Е. А.5, Sinitsyn V. Е.5, Vernokhaeva А. N.1, Bazaeva Е. V.1, Drapkina О. М.1, Boytsov S. А.6

Abstract

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.

Russ J Cardiol 2017, 10 (150): 100–106

dx.doi.org/10.15829/1560-4071-2017-10-100-106

Key words: Friedreich cardiomyopathy, Friedreich ataxia, cardiomyopathies, myocardial hypertrophy, heart failure, sudden cardiac death, non-compaction myocardium of the left ventricle.

1National Research Center for Preventive Medicine of the Ministry of Health, Moscow; 2Medical and Genetic Scientific Center, Moscow; 3Medical and Genetic Scientific Center, Moscow; 4Moscow Regional Research and Clinical Institute (MONIKI), Moscow; 5Treatment and Rehabilitation Center of the Ministry of Health, Moscow; 6SMRC of Cardiology of the Ministry of Health, Moscow, Russia.

GENOTYPES AND SERUM LEVELS OF APOLIPOPROTEIN E AND PARAOXONASE 1 IN CALCIFIC AORTIC

VALVE STENOSIS

Shcheglova E. V.1, Laipanova A. I.1, Baikulova M. K.2, Chotchaeva Z. K.1, Rogova S. S h.1, Kolesnikov V. N.2, Boeva O. I.1

Abstract

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.

Russ J Cardiol 2017, 10 (150): 107–112

dx.doi.org/10.15829/1560-4071-2017-10-107-112

Key words: apoliporotein E, paraoxonase 1, gene polymorphism, calcific aortic stenosis.

1Stavropol State Medical University, Ministry of Healthcare of the Russian Federation, Stavropol; 2Regional Clinical Center of Cardiology, Stavropol, Russia.

CLINIC AND PHARMACOTHERAPY

THE PROTOCOL: INFLUENCE OF THE COMBINATION CARRIAGE СУР2С19*2 AND *17 ON EFFICACY

OF CLOPIDOGREL

Zelenskaya Е. М.1, Barbarash О. L.2, Ganyukov V. I.2, Kochergin N. А.2, Apartsin К. А.3,4, Gorokhova А. V.3, Papeshina S. А.3, Nikolaev К. Yu.5,6, Batueva К. Yu.7, Yankovskaya S. V.6, Tronin А. V.1, Lifshits G. I.1,4,6

Abstract

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.

Russ J Cardiol 2017, 10 (150): 113–117

dx.doi.org/10.15829/1560-4071-2017-10-113-117

Key words: CYP2С19, clopidogrel, stent thrombosis.

1Institute of Chemical Biology and Fundamental Medicine of SD RAS, Novosibirsk; 2Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo; 3Irkutskaya Oblast Clinical Hospital of the “Sign of Honour” Award, Irkutsk; 4Irkutsk Scientific Center of SD RAS, Irkutsk; 5SRI of Therapy and Prevention Medicine — branch of SD RAS, Novosibirsk; 6Novosibirsk National Research State University, Novosibirsk; 7Surgut State University, Surgut, Russia.

HEMODYNAMIC STABILITY OF HYPERTENSION PATIENT: TRIPLE THERAPY OPPORTUNITIES

Poteshkina N. G.1,2, Krylova N. S.1,2, Svanadze А. М.1,2, Troshina А. А.1,2

Abstract

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.

Russ J Cardiol 2017, 10 (150): 118–123

dx.doi.org/10.15829/1560-4071-2017-10-118-123

Key words: arterial hypertension, coronary heart disease, heart failure, stroke, chronic kidney disease, triplixam.

1N. I. Pirogov Russian National Research Medical University (RNRMU), Moscow; 2CCH № 52 of the Department of Health, Moscow, Russia.

HOW TO REDUCE GASTROINTESTINAL BLEEDING RISK ON ANTICOAGULATION THERAPY IN NON-VALVULAR ATRIAL FIBRILLATION?

Baranova E. I.1,2, Filatova А. G.1, Ionin V. А.1

Abstract

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.

Russ J Cardiol 2017, 10 (150): 124–132

dx.doi.org/10.15829/1560-4071-2017-10-124-132

Key words: atrial fibrillation, anticoagulants, gastrointestinal bleeding risk, fibroeso phagogastroduodenoscopy.

1I. P. Pavlov First Saint-Petersburg state Medical University, Saint-Petersburg; 2Federal Almazov North-West Medical Research Centre of the Ministry of Health, Saint-Petersburg, Russia.

LECTURE

ESSENTIAL SYSTEMIC HYPERTENSION: GENETICS, CLINICS, EXPERIMENT

Markel А. L.1,2

Abstract

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.

Russ J Cardiol 2017, 10 (150): 133–139

dx.doi.org/10.15829/1560-4071-2017-10-133-139

Key words: essential hypertension, clinical data, evolution origin, genetic determination.

1FRC Institute of Cytology and Genetics SD RAS, Novosibirsk; 2Novosibirsk State University, Novosibirsk, Russia.

LITERATURE REVIEW

STRUCTURAL VARIABLITY OF LEUCOCYTE GENOME AND ARTERIAL CELLS IN HUMAN

ATHEROSCLEROSIS

Sleptsov А. А.1, Nazarenko M. S.1,2,3, Puzyrev V. P.1,3

Abstract

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.

Russ J Cardiol 2017, 10 (150): 140–146

dx.doi.org/10.15829/1560-4071-2017-10-140-146

Key words: atherosclerosis, CNV, DNA areas copies variation, microchips, biomarkers, diagnostics.

1SRI of Medical Genetics, Tomsk National Research Center of RAS, Tomsk; 2SRI of Complex Issues of Cardiovascular DIseases, Tomsk; 3Siberian State Medical University (SSMU), Tomsk, Russia.

JUBELEE

David M. Aronov

Russ J Cardiol 2017, 10 (150): 147–148

Jan L. Gabinskiy

Russ J Cardiol 2017, 10 (150): 149–150

24 ноября 2017 г.
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