[Dynamics of left ventricular longitudinal function in patients with arterial hypertension during therapy with angiotensin converting enzyme inhibitor moexipril].

AIM: To assess left ventricular longitudinal systolic and diastolic function in patients with arterial hypertension in whom regression of left ventricular (LV) hypertrophy (LVH) occurred at the background of long term therapy with angiotensin converting enzyme inhibitor moexipril and hydrochlorothiazide. MATERIAL AND METHODS: Analysis was fulfilled in 44 patients (age 51.76+/-5.58 years) with regression of concentric LVH after 12 months of therapy. Complex examination included tissue Doppler imaging of myocardium and 24-hour blood pressure monitoring. RESULTS: Decrease of myocardial mass (mean 60.26+/-35.92 g) was accompanied with positive dynamics of parameters of 24-hour blood pressure monitoring. We observed decrease of ivrtm from fibrous annulus of mitral valve at the site of interventricular septum, posterior, inferior, and anterior LV walls--in 38 patients (86.4%); increase of motion velocity of mitral valve fibrous annulus during early LV filling at the site of interventricular septum, inferior and lateral LV walls--in 32 patients (72.72%); elevation of systolic velocity of mitral valve fibrous annulus movement at the site of interventricular septum-- in 21 patients (47.73%), and at the site of LV posterior wall--in 28 patients (63.64%). In 35 patients (79.54%) number of segments with e/a <1.0 decreased from 11.41+/-4.42 to 7.92+/-2.81 (p=0.01). In 39 patients (88.64%) number of segments with ivrt >90 ms decreased from 12.73+/-3.67 to 7.33+/-3.54 (p=0.008). In 34 patients (77.27%) regression of LVH was accompanied with elevation of systolic velocity in basal and middle segments of lateral and inferior left ventricular walls.

[ACE and AGTR1 genes polymorphisms in left ventricular hypertrophy pathogenesis in humans]. / Polimorfizm genov ACE i AGTR1 v patogeneze gipertorofii levogo zheludochka serdtsa u cheloveka.

The role of A2350G polymorphism in exon 17 of the ACE gene and A1166C - in 3'-UTR of the AGTR1 in the pathogenesis of left ventricular hypertrophy was studied in patients with essential hypertension (EH) and arterial hypertension combined with diabetes mellitus type 2 (AH + DM2). Patients with EH and AH + DM2 did not differ from the control sample of healthy individuals by allele or genotype frequencies. However, an association of both polymorphisms with LVH was detected in EH patients. The frequency of 1166C allele was higher in patients with LVH (33.6% vs 20.7% without LVH). A1166C polymorphism determined the magnitude of left ventricular mass index (LVMI) in EH patients as well (p = 0.007). 2350G allele frequency of the ACE gene was in 1.5, and GG genotype--in 3.5-fold higher in EH patients with LVH, as compared without LVH. LVMI was significantly higher in patients with GG genotype as compared with heterozygotes and AA homozygotes (p = 0.002). Thus the presence of 1166C allele of AGTR1 and 2350G allele of ACE can be considered as predisposing factors for LVH development in EH. In contrast, association of studied polymorphisms with presence or LVH degree was not detected in patients with arterial hypertension combined with DM2. This may indicate another structure of genetic component of predisposition to LVH in different causes.

[Polymorphic markers of GNB3 (C825T), AGTR1 (A1166C) and ACE (A2350G and I/D) genes in patients with arterial hypertension combined with diabetes mellitus type 2]. / Polimorfnye markery genov GNB3(C825T), AGTR1(A1166C), and ACE(A2350G and I/D) u bol'nykh arterial'noi gipertoniei, sochetaiushcheisia s sakharnym diabetom tipa 2.

AIM: To elicit correlations of polymorphic markers of GNB3 (C825T), AGTR1 (A1166C), ACE (A2350G and I/D) genes with arterial pressure, left ventricular hypertrophy (LVH) and blood concentrations of proinflammatory cytokines in hypertensive patients with diabetes mellitus type 2 (DM2). MATERIAL AND METHODS: Clinical parameters (24-h arterial pressure profile, echocardiographic findings, immunoenzymes level) were studied in 89 hypertensive patients with DM2. These patients had different genotypes by the studied allele variants of the genes determined by polymerase chain reaction. RESULTS: Polymorphism of A1166C gene of type 1 vascular receptor of angiotensin II (AGTR1) contributes to formation of arterial hypertension (AH) signs diversity in DM2 patients. GNB3, a gene C825T polymorphic marker, showed a correlation with diastolic arterial pressure but this variant of the gene locus is not associated with LVH. However, G-allele of ACE gene contributes much to appearance of this pathological sign. Mean values of IL-1beta and TNF-alpha as well as the presence of LVH depended on genotypes by ACE gene (polymorphism I/D). CONCLUSION: Polymorphic markers of ACE and GNB3 candidate genes influence clinical diversity of pathological signs in DM2 patients through modification of AH and LVH severity and the level of proinflammatory cytokines.

[MtDNA and Y-chromosome lineages in the Yakut population]. / Linii mtDNK i Y-khromosomy v populiatsii iakutov.

The structure of female (mtDNA) and male (Y-chromosome haplotypes) lineages in the Yakut population was examined. To determine mtDNA haplotypes, sequencing of hypervariable segment I and typing of haplotype-specific point substitutions in the other parts of the mtDNA molecule were performed. Y haplogroups were identified through typing of biallelic polymorphisms in the nonrecombining part of the chromosome. Haplotypes within haplogroups were analyzed with seven microsatellite loci. Mitochondrial gene pool of Yakuts is mainly represented by the lineages of eastern Eurasian origin (haplogroups A, B, C, D, G, and F). In Yakuts haplogroups C and D showing the total frequency of almost 80% and consisting of 12 and 10 different haplopypes, respectively, were the most frequent and diverse. The total part of the lineages of western Eurasian origin ("Caucasoid") was about 6% (4 haplotypes, haplogroups H, J, and U). Most of Y chromosomes in the Yakut population (87%) belonged to haplogroup N3 (HG16), delineated by the T-C substitution at the Tat locus. Chromosomes of haplogroup N3 displayed the presence of 19 microsatellite haplotypes, the most frequent of which encompassed 54% chromosomes of this haplogroup. Median network of haplogroup N3 in Yakuts demonstrated distinct "starlike phylogeny". Male lineages of Yakuts were shown to be closest to those of Eastern Evenks.

[Genetic peculiarity of the yakut population from the autosomal loci data]. / Geneticheskoe svoeobrazie naseleniia Iakutii po dannym autosomnykh lokusov.

The autosomal gene pool of Yakuts was analyzed with a panel of polymorphic Alu insertions. The observed allele frequencies were typical for other Asian ethnic groups. Genetic differentiation of three Yakut populations was relatively high, 2%. East Siberian ethnic groups were shown to have a common gene pool and to experience no intense gene flow from other populations. Development of the Yakut gene pool was assumed to involve no substantial genetic effect of neighboring populations. The results fit both autochthonous and southern origin hypotheses.

[The relationship between the 24 hour arterial pressure profile with heart changes in patients with essential hypertension]. / Vzaimosviaz' sutochnogo profilia arterial'nogo davleniia s izmeneniiami serdtsa u bol'nykh s éssentsial'noi gipertenziei.

A 24-h profile of arterial pressure (AP), structural-geometrical changes of the left ventricle (LV) and severity of hypertensive heart were compared in 47 patients with essential hypertension. Absolute AP and LV geometric models were not related. In patients with concentric LV hypertrophy, the time index (TI) of night systolic hypertension was significantly higher than TI in excentric LV hypertrophy. A relationship was found between mean day systolic pressure, a morning rise in AP and form of LV hypertrophy. The severity of hypertensive heart correlated with TI of 24-h systolic arterial pressure (SAP), TI of 24-h diastolic arterial pressure (DAP), mean 24-h SAP, mean daytime SAP, mean night SAP, mean 24-h DAP, mean daytime DAP, a morning rise in DAP. Thus, a 24-h AP profile, a morning rise in DAP, 24-h hypertension time correlate with LV structural-geometric changes and severity of hypertensive heart.

[Genomic studies of hereditary cardiomyopathies]. / Genomnye issledovaniia nasledstvennykh kardiomiopatii.

Cardiomyopathies (CMP) clinically and genetically belong to the heterogeneous group of myocardial diseases. Among them, three major clinical forms (hypertrophic, dilated, and restricted) are distinguished. Genetic factors play a substantial role in the etiology of dilated and hypertrophic CMP; family cases constitute more than 20% of these forms. Most familial cases of CMP are inherited as an autosomal dominant character. Autosomal recessive and X-linked forms are rare. Genetic basis for rare familial forms of restricted CMP is unclear. There are forms with strict maternal inheritance, which suggests the involvement of the mitochondrial genome. The nature of several CMP forms was determined and a number of genetic loci for this disease was revealed by modern methods of genetic mapping. In familial hypertrophic cardiomyopathy (FHC), four genes have been identified (those of beta-myosin heavy chain, alpha-tropomyosin, cardiac troponin T, and myosin-binding protein C), all of which encode sarcomeric proteins. Maternally inherited forms of FHC are associated with mutations in the mitochondrial tRNA genes. Linkage analysis in familial dilated CMP revealed at least five genetic loci on chromosomes 1, 3, 9, and X. X-linked forms of dilated CMP are caused by mutations in dystrophin gene, but the nature of autosomal forms is unclear. A recently recognized form of dilated CMP, arrhythmogenic CMP/right ventricular dysplasia (ARVD) is linked to two actinin gene loci on chromosomes 1 and 14. Genomic studies of CMP provided a basis for a new stage of "genetic cardiology", genetic mapping, which at present includes the quest of candidate genes for many other human cardiovascular diseases.

[Polymorphism of angiotensin-converting enzyme and endothelial nitric oxide synthase genes in people with arterial hypertension, left ventricular hypertrophy, and hypertrophic cardiomyopathy]. / Polimorfizm genov angiotenzin-prevrashchaiushchego fermenta i éndotelial'noi sintazy okisi azota u lits s arterial'noi gipertenziei, gipertrofiei levogo zheludochka i gipertroficheskoi kardiomiopatiei.

Data on polymorphism of the angiotensin-converting enzyme (ACE) and endothelial cell nitric oxide synthase (NOS3) genes in patients having arterial hypertension (AH) with or without left ventricular hypertrophy (LVH) and those with hypertrophic cardiomyopathy (HCM) are presented. An association between polymorphism for the ACE and NOS3 loci and the LVH index among AH patients with LVH and HCM was shown. In AH patients, an association between the NOS3 locus polymorphism and some parameters of blood pressure was revealed. Possible relationships between the ACE and NOS3 polymorphisms and the clinical manifestation of the LVH and AH are discussed.