[Association of rs3025058 polymorphism with the development of stroke in patients with cardiovascular pathology].

AIM: To study the association of single-nucleotide polymorphismrs3025058(5а/6а) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors for its development. MATERIALS AND METHODS: The study involved 260 patients with stroke (age [57.0; 51.062.0]) and 272 patients of the control group (age [55.0; 51.062.0]). Among the patients who underwent stroke, 157 men and 103 women. The control group included 170 men and 102 women. The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of the extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. The patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of extracranial brachiocephalic arteries, disorders of the hemostasis system. The control group was examined within the framework of the international project HAPIEE. Molecular genetic research was carried out by real-time PCR. Statistical processing of the material was carried out using the Statistica for Windows 7.0, Excel and SPSS 22 application software. RESULTS: The study established statistically significant associations between the 5a/5a genotype and the 5a allele and stroke in the general group of patients, as well as in the subgroup of men, subgroups of patients with extracranial brachiocephalic arteries atherosclerosis and dyslipidemia. In the subgroup of patients with cardiac arrhythmias, statistically significant results were obtained only for allele 5a, and in the subgroup of women with stroke, subgroups of patients with arterial hypertension and hypercoagulation, no significant associations ofrs3025058(5a/6a) polymorphism with stroke were found. CONCLUSION: Genotype 5a/5a and allele 5a of the single-nucleotide polymorphismrs3025058(5а/6а) increase the risk of stroke in individuals from the East Siberian population, including those in the presence of such risk factors as extracranial brachiocephalic arteries atherosclerosis and dyslipidemia.

Putative role of Brugada syndrome genes in familial atrial fibrillation.

OBJECTIVE: Familial atrial fibrillation (FAF), a not uncommon arrhythmia of the atrium, is characterized by heritability, early onset and absence of other heart defects. The molecular and genetic basis is still not completely clear and genetic diagnosis cannot be achieved in about 90% of patients. In this study, we present the results of genetic screening by next generation sequencing in affected Russian families. PATIENTS AND METHODS: Sixty subjects (18 probands and 42 relatives) with a clinical diagnosis of FAF were enrolled in the study. Since AF frequently associates with other cardiomyopathies, we included all genes that were known to be associated with these disorders at the time of our study. All probands were therefore systematically screened for 47 genes selected from the literature. RESULTS: Our study revealed that seven variants co-segregated with the clinical phenotype in seven families. Interestingly, four out of six genes and three out of seven variants have already been associated with Brugada syndrome in the literature. CONCLUSIONS: To our knowledge, this is the first report of association of the CACNA1C, CTNNA3, PKP2, ANK2 and SCN10A genes with FAF; it is also the first study in Russian families.

Association of SOCS5 gene polymorphism with allergic bronchial asthma.

AIM: To study the association of mononucleotide polymorphism rs6737848 SOCS5 gene with the risk of development of allergic bronchial asthma. MATERIALS AND METHODS: Totally 59 patients studied (19 males, 40 females) with allergic bronchial asthma and 50 healthy people (29 males, 21 females) of controls. All patients underwent clinical and instrumental and laboratory investigations in KICH №20 (Krasnoyarsk city) and molecular-genetic investigation of DNA in the Russia-Italian laboratory "MAGI" (Krasnoyarsk city) and Institution of Internal and Preventive Medicine (Novosibirsk city). Statistics included standard programs: Statistica for Windows 7.0. RESULTS: The results of the study showed statistical predominance of prevalent genotype СС of SOCS5 gene in allergic bronchial asthma patients, comparing to control group. CONCLUSION: Homozygous genotype of СС gene of SOCS5 is a risk factor for allergic bronchial asthma.

Polymorphisms of the SCN10A Gene in Patients With Sick Sinus Syndrome.

PURPOSE: To study association of rs6795970 polymorphism of SCN10A gene with development of idiopathic sick sinus syndrome (ISSS). MATERIALS AND METHODS: We examined 109 patients with ISSS, 59 their healthy 1-st-, 2-nd-, and 3-rd-degree relatives, and 630 controls. Patients with ISSS were divided into subgroups according to gender and clinical variant of the disease. All patients underwent cardiologic examination and molecular genetic testing of DNA. RESULTS: We revealed significant preponderance of homozygous genotype with rare allele of the studied gene among patients with ISSS compared with control group. In addition, this genotype significantly prevailed among men with SSSU in comparison with the control group. CONCLUSION: Genotype AA of the SCN10A gene is associated with a predisposition to the development of ISSS.

[Role of AGTR1 A/C polymorphism in the development of atrial fibrillation]. / Rol' polimorfizma A/C gena AGTR1 v razvitii fibrilliatsii predserdii.

AIM: To investigate the AGTR1 A/C polymorphism associated with atrial fibrillation (AF) to form risk groups among patients who are prone to this disease. SUBJECTS AND METHODS: 90 probands with a confirmed diagnosis of AF and their 144 first-, second-, and third-degree relatives were examined. These families made up a study group. A control group was formed of 100 apparently healthy individuals without a history of cardiovascular diseases. Collection of medical history data and complaints, electrocardiography, electrocardiogram monitoring, as well as molecular genetic analysis, thyroid hormone tests were done in all the patients. RESULTS: No statistically significant data on the correlation between the AGTR1 A/C polymorphism and the development of AF were obtained in any patient subgroup. The obtained results can be due to the genetic features of a Siberian population, which are dependent on climatic conditions and geographical location, and confirm that AF is a heterogeneous disease. CONCLUSION: There were no statistically significant differences between the patients in the study group and those in the control group. Our findings suggest the heterogeneity of AF and confirm its multifactorial nature.

TNFR1 -383 A˃C polymorphism and ankylosing spondylitis in a Russian Caucasian population: a preliminary study.

The aim of this study was to assess the association between the TNFR1 rs2234649 polymorphism and ankylosing spondylitis susceptibility in a Russian Caucasian population. A total of 41 ankylosing spondylitis patients and 43 healthy controls, matched according to age and sex, were enrolled, and polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the rs2234649 variant. We evaluated genotype distributions in the patient and control groups with the chi-square test, and assessed the relationship between genotypes and ankylosing spondylitis using the odds ratio. Our analysis showed that the rs2234649 polymorphism does not increase ankylosing spondylitis risk. In conclusion, the TNFR1 gene polymorphism tested does not appear to be useful for assessing predisposition to this disease or for its diagnosis or prognosis.

Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion. This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance. Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work. The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue. Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores. No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS. In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS.

[The Role of Transcriptional Factor Gene TBX5 in Development of Disorders of Cadiac Conduction].

In order to study relationship between development of idiopathic atrioventricular (AV) and intraventricular disorders of cardiac conduction (DCC) with single nucleotide polymorphism (SNP) of TBX5 gene we examined 260 persons with primary DCC (71 patients with abnormal AV conduction, 84 and 105 patients with disordered conduction along right and left brunches of His bundle, respectively) as well as 257 individuals without cardiovascular diseases (control group). Patients were divided into subgroups depending on nosology, age, and sex. Diagnosis was verified by standard cardiological methods and retrospective analysis of available results of previous examinations. Molecular-genetic study of DNA was used for identification of genotype of TBX5 gene SNP. The results indicated significant preponderance of rare GG genotype (CNP-marker rs3825214) of TBX5 gene in the group of patients with left bundle branch block and in the subgroup of women with this pathology. These data suggest that presence of GG genotype (rs3825214) of TBX5 gene increases probability of development of idiopathic DCC along left bundle branch mainly in women.

[Polymorphic alele variants of eNOS gene in patients with disorders of cardiac conduction].

We studied the role of endothelial nitric oxide synthase gene polymorphism 4a/4b in development of such disturbances of cardiac conduction as atrioventricular (AV) block and sick sinus node syndrome (SSNS). We examined 69 subjects (36 men, 33 women) with AV block and 90 subjects (33 men and 57 women) with SSNS. They were divided into groups in dependence on type of conduction disorder and sex. Probands with pathologies studied composed separate groups. All participants underwent included clinical-instrumental cardiological examination and molecular genetic study of eNOS gene polymorphisms. In all groups we revealed significant predominance of a rare homozygous genotype 4b/4b and tendency to decreased number of carriers of widely spread 4a/4a allele.

[The role of alfa-2-beta-adrenoreceptor in development of ventricular conduction disturbance].

BACKGROUND: The purpose of this study was to investigate association between the genetic polymorphism I/D of gene α2ß-adrenoreceptor (ADRA2B) and hereditary disorders of ventricular conduction. PATIENTS AND METHODS: In this study, 102 people with complete left bundle branch block (45.71 ± 1.852 years)--46 females and 56 males, and 86 people with complete right bundle branch block (34.59 ± 1.86 years)--41 females and 45 males. The study was approved by Ethic Committee of the KrasSMU. All participants were included in the study after written informed consent form. Cardiological examination included clinical examination, electrocardiography, echocardiography, Holter monitoring, stress-test, koronaroangiografy and radionuclide method of a myocardium and molecular and genetic researches. RESULTS: Statistically, significant prevalence of a homozygous genotype of DD on rare allele gene ADRA2B in both groups in comparison with group of control is established. The reliable dominance of the homozygous rare genotypes (D allele) of gene ADRA2B were detected in all groups. CONCLUSION: Polymorphism DD of a gene ADRA2B is a genetic predictor of predisposition to the blockade of the right and left bundle branch block.

[Genetic predictors of myocardial infarction in subjects of young age].

AIM OF THE STUDY: to investigate associations of single nucleotide polymorphisms (SNP) rs499818 (6p24.1), rs619203 of ROS1 gene (6q22), rs10757278 rs1333049 (9p21.3), rs2549513 (16q23.1), rs4804611 of ZNF627 gene (19p13.2) with myocardial infarction in subjects of young age. The group of patients with MI (n=99) aged less than 45 years and the control group (n=111) did not differ significantly by sex (=0,617), age (=0.291), arterial hypertension (=0.766), diabetes mellitus (=0.395), hypercholestolemia (=0.696), excessive body mass and obesity (=0.361), abdominal obesity (=0.831) and history of smoking (=0.400). There was significant difference between groups by burdened heredity (<0.001). Genomic DNA was obtained from venous blood by phenol-chloroform extraction. Genetic testing was performed by real time polymerase chain reaction using 7900HT Fast Real-Time PCR System according to manufacturers protocol. We found significant association between rs1333049 and rs10757278 and myocardial infarction (MI). Odds ratio (OR) of development of MI in carriers of risk allele rs1333049 was 2.4 (95% confidence interval [CI] 1.24 to 4.65), in carriers of G rs10757278 allele - 2.00 (95%CI 1.05 to 3.80). Association of risk alleles rs 1333049 and G rs10757278 with MI remained significant after adjustment for burdened family history (OR 4.25, 95%CI 1.39 to 12.99, and OR 3.04, 95%CI 1.09 to 8.52, respectively). Presence in the genotype of both risk alleles rs1333049 and G rs10757278 was associated with OR of MI development 2.40 (95%CI 1.20 to 4.82) which was not different from that associated with carriage of allele rs1333049 only. Possibly in our population both SNPs belong to one linkage block and correspondingly it is sufficient to genotype one SNP. No significant associations with MI were found for variants rs4804611, rs2549513, rs499818, rs619203. SNPs rs1333049 and rs10757278 of 9p21.3 locus are predictors of MI in young individuals not dependent on both traditional risk factors and presence of burdened family history.

[α-2ß-adrenoreceptor gene polymorphism in patients with disorders of cardiac conduction].

The article is devoted to the role of insertion-deletion polymorphism of -2-adrenoreceptor gene in development of hereditary disorders of cardiac conduction. We examined 71 patients with atrioventricular blocks and 92 patients with sick sinus node syndrome. Statistically significant preponderance of homozygous genotype DD of ADRA2B gene was found in both groups. Associations of alleles with male or female gender were also revealed.

[Genetic predictors of sick sinus node syndrome].

The article is devoted to the role of heredity in development of the sick sinus node syndrome (SSNS). We have examined 14 probands and 110 their relatives from families with idiopathic SSNS and established the role in development of hereditary SSNS of polymorphisms of the following genes: -2-adrenoreceptor, enzyme endothelial NO synthase, protein connexin 40, voltage dependent cardiac sodium channels, cardiac myosin heavy chains. We also revealed associations of clinical variants of idiopathic SSNS with genotypes of the studied genes.

[Interrelationship between polymorphic markers of methylenetetrahydrofolate reductase gene and development of acute disturbance of brain circulation in families of patients with atrial fibrillation].

In the present work we for the first time on the clinic-genetic material revealed genetic predictors of development of acute disturbance of brain circulation (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was significantly more often found among patients with AF and ADBC compared with controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of probands compared with the control group (59.3 and 35.2%, respectively, p=0.008). With this in relatives with revealed paroxysmal AF and ADBC we also noted presence of CC genotype. Taking into consideration the relationship obtained between polymorphysms of MTHFR gene and AF it was possible to assume that polymorphic marker CC appeared to be a predictor of ADBC in these families.

[Association of 2B-adrenergic receptor gene polymorphism with disturbances of cardiac conduction].

In this work we for the first time revealed on clinical - genetic material association between hereditary disturbances of cardiac conduction and polymorphism of 2-adrenergic receptor gene.

[Polymorphisms of 2B-adrenergic receptor and endothelial NO-Synthase genes in genesis of the hereditary sick sinus node syndrome].

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome (SSNS) ADRA2B and eNOS genes polymorphisms. We have established predominance of homozygote genotype of more rare DD allele in patients with SSNS (28%) compared with subjects of control group (8.99%). We have found predominance of heterozygote genotype 4a/4b in patients with SSNS compared with subjects of control group (41.8 and 25.39%, respectively). The data obtained allow to suggest that eNOS gene polymorphism might be associated with SSNS.