[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.

[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.

[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.

[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 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.

[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.

[Polymorphism of connexin 40 gene-- a novel genetic marker of the 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 and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

[Improvement of higher medical education via the system of quality specialist training].

Development of the system of management of quality specialist training in the Kraysnoysrsk State Medical Academy allowed to optimize administration and academic process, create conditions for introduction of innovative technologies in educational, research, and clinico-diagnostic activities for the purpose of their standardization and realization of managerial decisions. The new system promotes organization of administrative and educational work of the Academy in line with leading trends of regional development, stimulates creativity and strategic planning.

[Ser49gly polymorphism as predictor of development of hereditary sick sinus node syndrome].

We demonstrated for the first time on clinico-genetic material an association of hereditary sick sinus node syndrome (SSNS) with polymorphism of beta-adrenorecetor gene. We found that heterozygous variant of Ser49gly of beta-adrenoreceptor gene was significantly more often met in patients with SSNS and their healthy relatives than in subjects of control group. In the group of patients with SSNS contrary to control group we noted statistically significant preponderance of carriers of mutant Gly49 allele of.

[Genetics of atrial fibrillation].

We carried out examination of 103 probands with atrial fibrillation (AF) and 301 their 1st, 2nd, and 3rd degree relatives (main group). In addition we examined 82 probands without clinical electrocardiographic signs of heart disease and 163 their 1st and 2nd degree relatives (control group). We found accumulation of AF in families of probands with this pathology. Segregation analysis of idiopathic forms of AF allowed to reveal autosomal dominant type of inheritance of this pathology. Heterozygous variant of Ser49Gly of betai-adrenoreceptor gene can be considered as one of genetic predictors of development of how primary and secondary AF.

[Clinical and genetic features in patients with asthma and their relatives].

A familial survey was conducted in 81 probands who were diagnosed as having bronchial asthma (BA) and their 183 first-, second-, and third-degree relatives (a study group). A control group comprised 263 apparently healthy individuals. The familial accumulation of BA was ascertained in the families of probands with this condition. Autosomal dominant inheritance of BA was established. The heterozygous variant of the macrophage-colony-stimulating factor receptor (MCSFR) gene genotype chi-fms may be considered as one of the genetic predictors of BA. The homozygous genotype in a rare allele of the MCSFR gene may be also a predictor of BA.

[Angiotensin-converting enzyme gene polymorphism in patients with primary disturbances of cardiac conduction]. / Polimorfizm gena angiotenzinprevrashchaiushchego fermenta u bol'nykh s narusheniiami serdechnoi provodimosti.

Increased frequencies of angiotensin-converting enzyme (ACE) D-allele and ID-genotype among patients with idiopathic atrioventricular blocks and I allele and II genotype among patients with idiopathic intraventricular blocks allow to consider these genotypes risk factors of corresponding disturbances of cardiac conduction. Decreased frequency of ACE I allele and II genotype among patients with idiopathic atrioventricular blocks is indicative of a possible protective role of II genotype against development of this type of cardiac conduction defect. Low frequency of D allele and genotype D prevents derangements of conduction in His-Purkinje system.

[New data on etiology of heart conduction disturbances]. / Novoe ob étiologii narushenii vnutriserdechnoi provodimosti.

AIM: To make a clinicogenealogical analysis of different types of heart conduction disturbances in families of Krasnoyarsk city. MATERIALS AND METHODS: 104 probands with ECG-verified idiopathic forms of atrioventricular and intraventricular blocks of different severity and 331 their close relatives (kinship degree I and II) were examined using standard clinical investigations, ECG, echocardioscopy, electrophysical investigations in some cases and coronarography. RESULTS: All the observed 104 families were divided into 3 groups according to the type of heart conduction in proband. Group 1 consisted of 24 probands with atrioventricular block and 80 their relatives. The sick relatives had for the most part atrioventricular blocks (31.2%). 26 probands of group 2 had complete right bundle branch blocks. Of their 81 relatives, the sick ones had primarily conduction disturbances in right bundle branch (incomplete block--44.7%, a complete block--5.2%). Group 3 consisted of 54 probands with left bundle branch block and 170 relatives. The left bundle branch block was present in 27.4% of the relatives. CONCLUSION: A definite family aggregation of heart conduction disturbances was found. This proves genetic determination of this pathology.

[Relationship between polymorphism of non-coding regions of human mitochondrial genome and primary cardiac conduction disorders]. / Sviaz' polimorfizma nekodiruiushchikh oblastei mitokhondrial'nogo genoma cheloveka s pervichnymi narusheniiami serdechnoi provodimosti.

AIM: Analysis of associations between idiopathic disturbances of cardiac conduction (DCC) and polymorphism of mitochondrial genome. MATERIAL AND METHODS: A family examination was performed in 431 probands with various DCC and 1347 relatives of the first, second and third degree of kinship (the study group). All the examinees were divided into four subgroups. These included 158 probands with atrioventricular block (AVB) of various degree and their 518 relatives (subgroup 1); 50 probands with a complete right bundle-branch block (BBB) and their 161 relatives (subgroup 2); 108 probands with a complete left BBB and left anterior branch of the His bundle and their 152 relatives (subgroup 3); 115 probands with sick sinus syndrome (SSS) and their 327 relatives (subgroup 4). The control group consisted of 104 probands without clinical ECG manifestations of cardiac diseases and their 321 relatives. All the examinees have undergone ECG, atropin test, echocardioscopy, electrophysiological examination of the heart and mitochondrial DNA (mDNA). RESULTS: Comparison of the incidence of mDNA D-loop restriction sites in the group of patients with idiopathic DCC and controls has found higher frequency of the Hae III 16517 site in the group of the patients (p = 0.0480). By location of the blocks (atrioventricular and intraventricular), the site occurred more frequently in patients with AVB (86.36%). The variant "+" by the site of Hae III 16517 mDNA was found to associate with disturbances of cardiac conduction, more closely in AVB. CONCLUSION: Variability of mDNA may be an etiological factor of idiopathic DCC pathogenesis.

[The etiological aspects of the sick sinus syndrome]. / Nekotorye étiologicheskie aspekty sindroma slabosti sinusovogo uzla.

A clinico-genetic study of sick sinus syndrome in Krasnoyarsk population established its prevalence as 0.296%. The disease affected females more frequently than males. The highest morbidity was registered at the age 60-69. Genetic evaluation demonstrated high hereditary predisposition to the syndrome as it developed in 60 out of 309 (19.4%) relatives of the patients, the inheritance being autosomal dominant and in part sex-limited. Females predominated among the disease-affected relatives and among those whose relatives had the syndrome. The syndrome is also age-related. The authors discuss the role of ischemic heart disease in the origin of sick sinus syndrome.