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The pathogenesis of atherosclerosis and ischemic heart disease is associated with oxidative stress and mitochondrial dysfunction. Mitochondrial DNA encodes subunits of mitochondrial respiratory chain and is highly polymorphic in human populations. Mitochondrial DNA can be considered a candidate genetic locus for predisposition to cardiovascular diseases.Aim. To analyze the associations of the mitochondrial genome polymorphism and chronic heart failure in ischemic heart disease.Material and Methods. The study included two groups of individuals: patients with a combination of ischemic heart disease and chronic heart failure (n = 175) and a population sample of residents of Tomsk (n = 424). Percentages of patients with chronic heart failure of NYHA classes II, III, and IV were 37%, 50%, and 13%, respectively. All patients underwent echocardiographic examination; body mass index and the lipid fractions in blood serum were determined. The average was 55.4 years in patients and 47.6 years in the population sample. Polymorphism of mtDNA was studied by sequencing the hypervariable segment of D-loop of mtDNA and subsequent classification of mtDNA haplotypes into the known haplogroups. The mtDNA haplogroup frequencies were compared between the samples using the Chi-square test. The associations of genotype with quantitative trait variability were analyzed by variance analysis.Results. Male patients showed a higher frequency of haplogroup H compared to the population (45.86% in patients and 35.4% in population) and a higher total frequency of haplogroup H subgroups except the most frequent subgroup H1 (36.94% and 25.22%, respectively). The values of significance level (p-value) and odds ratio (OR) were determined as follows: p = 0.04; odds ratio OR = 1.55 (95% confidence interval (CI) 1.02–2.34) for haplogroup H as a whole; p = 0.02; OR = 1.74 (95% CI 1.12–2.70) for haplogroup H without subgroup H1. Analysis of quantitative traits revealed the associations of the same genetic marker (mtDNA haplogroup H) with the levels of high-density lipoproteins (p = 0.03) and triglycerides (p = 0.02) in blood serum of men in the population sample.Conclusion. The obtained results suggested that the most frequent European mtDNA haplogroup H may be a risk factor for the complications of ischemic heart disease in men.

Brugada syndrome (BrS) is an inherited disorder characterized by specific ST segment elevation in the right precordial leads, pseudo right bundle branch block, and a high risk of sudden cardiac death due to ventricular tachycardia. It was initially described as a monogenic disorder with an autosomal dominant mode of inheritance. It is hypothesized that modifying genetic factors, in addition to disease-causing mutations, may significantly contribute to the clinical symptoms and the risk of sudden cardiac death. These modifying factors can include mitochondrial DNA (mtDNA) variants. In particular, combination of mtDNA m.T4216C, m.A11251G, m.C15452A and m.T16126C variants (defining haplogroups T and J), is considered to be a factor that promotes manifestation of BrS manifestation, with no pro-arrhythmic effects. The aim of the present study was to confirm the reported association of BrS with MtDNA variants in a cohort of Russian patients. mtDNA haplogroups were genotyped in 47 Russian BrS probands and the prevalence of common mtDNA haplogroups was compared with the general population in European part of Russia. The distribution and prevalence of all but the J mtDNA haplogroups were comparable in BrS probands and the general Russian population. The mitochondrial J haplogroup was not found in the BrS cohort. In conclusion, it was shown that the mtDNA polymorphism, m.T4216C (haplogroups J and T) does not contribute significantly to the clinical manifestation of BrS in Russian patients.

For identification of somatic mitochondrial DNA (mtDNA) mutations, the mtDNA major noncoding region (D-loop) sequence in blood samples and carotid atherosclerosis plaques from patients with atherosclerosis was analyzed. Five point heteroplasmic positions were observed in 4 of 23 individuals (17%). Only in two cases could heteroplasmy have resulted from somatic mutation, whereas three heteroplasmic positions were found in both vascular tissue and blood. In addition, length heteroplasmy in a polycytosine stretches was registered at nucleotide positions 303-315 in 16 individuals, and also in the 16184-16193 region--in four patients. The results suggest that somatic mtDNA mutations can occur during atherosclerosis, but some heteroplasmic mutations may appear in all tissues, possibly being inherited.

Aim to study associations of polymorphic genetic variants of inflammatory response, endothelial function, lipid metabolism, and blood coagulation with impaired renal function in patients with ST elevation myocardial infarction (STEMI). Material and methods We enrolled in the study 171 patients admitted to the Kemerovo Cardiology Dispensary within 24 hours after onset of STEMI. All patients underwent genotype identification of 25 polymorphic variants of 18 major candidate genes for cardiovascular disease. Genotyping was performed with DNA chip SINKAR-1 (Institute of Medical Genetics and LLC "Genomic Diagnosis"). Glomerular filtration rate (GFR) was estimated using serum creatinine level measured at admission. Results Comparison of allelic and genotype frequencies of the studied polymorphisms revealed that angiotensin-converting enzyme (ACE) gene rs4291 was associated with decreased GFR: odds ratio (OR) for carriers of rare TT genotype was 2.31 [1.01-5.25], =0.043. Analysis of genotype combinations of ACE rs4343 polymorphism and hepatic lipase gene (LIPC) rs1800588 showed that AA genotype of rs4343 polymorphism in combination with CC genotype of rs1800588 polymorphism was associated with lowest risk of renal dysfunction, whereas GG and AG genotypes of ACE rs4343 in combination with TT and CT genotypes of LIPC rs1800588.

A group of patients with ischemic heart disease and myocardial infarction (N = 156) and a reference population sample (N = 300) were genotyped for 58 single nucleotide polymorphisms (SNPs) in the genes involved in extracellular matrix function and collagen metabolism or associated with cardiovascular diseases and atherosclerotic plaque stability. Genotyping was performed by mass-spectrometry with two multiplex sets of 27 and 31 SNPs. The study revealed different genetic composition of predisposition to cardiovascular disease continuum (CVDC) syntropy (patients with concomitant conditions: hypercholesterolemia, hypertension, and type-II diabetes mellitus, N = 96) and to isolated myocardial infarction (without these conditions, N = 60). Only the KIAA1462 gene (rs3739998) showed associations with both CVDC syntropy (OR = 1.71; 95% CI 1.19-2.45; р = 0.003) and isolated infarction (OR = 1.58; 95% CI 1.05-2.40; р = 0.028). Isolated myocardial infarction was also associated with LIG1 (rs20579) (OR = 2.08; 95% CI 1.06-4.17; р = 0.028) and ADAMDEC1 (rs3765124) (OR = 1.63; 95% CI 1.07-2.50; р = 0.020). CVDC syntropy was associated with CDKN2BAS1 (rs1333049) (OR = 1.48; 95% CI 1.03-2.12; р = 0.029) and APOA2 (rs5082) (OR = 1.47; 95% CI 1.02-2.11; р = 0.035). So, genes involved in fibrogenesis contribute to predisposition to the myocardial infarction as well. Isolated myocardial infarction and CVDC syntropy can be considered as pathogenetically different cardiovascular conditions, with different genes that contribute to the susceptibility.

We performed an association analysis for the mtDNA major common variants and haplogroups with incidence of myocardial infarction and essential prognostic characteristics in patients. A comparison of patients (N = 406) and control groups (N = 183) uncovered a higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p = 0.033). Patients with early infarction (before age of 55 in men) had a higher frequency of 16189C variant, compared to patients who endured first infarction at age older than 55 (24.1% vs. 12.5%; p = 0.008). In addition, haplogroup U2e was only detected in the subgroup with early infarction (4.4%; p = 0.004). Haplogroup U5 was less frequent in patients with early infarction (5.1% vs. 15.4%; p = 0.002). Observations during a 1-year follow-up uncovered that patients with recurring cardiovascular incidents had higher frequency of haplogroup H1 (20%, versus 4.5% in patients without complications, p = 0.002) and variant 16189C (30% versus 13.5%; p = 0.018). Haplogroup U5 was more frequent in the subgroup of patients with lower (

We have performed association analysis for mtDNA most common variants and haplogroups with myocardial infarction and some prognostic characteristics in patients. Comparison of patients (N=406) and controls (N=183) has shown higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p=0.033). Patients with early infarction (before age 55), comparing to patiens older than 55 and the first infarction, had higher frequency of 16189C variant (24.1 vs. 12.5%; p=0.008); also, haplogroup U2e was registered only in the subgroup with early infarction (4.4%; p=0.004). On the other side, haplogroup U5 was less frequent in the patients with early infarction (5.1% vs. 15.4%; p=0.002). The patients with recurring cardiovascular incidents during one year follow-up had higher frequency of haplogroup H1 (20% versus 4.5% in the patients without complications, p=0.002) and variant 16189C (30% versus 13.5%; p=0.018). Haplogroup U5 was more frequent in the group of patients with left ventricular ejection fraction less than 40%: 17.1% comparing to 8.2% in the group with ejection fraction>40%; p=0.034. The results suggest that mtDNA polymorphism contributes to coronary atherosclerosis. The associations could be explained by the polymorphism effect on oxidative phosphorylation and reactive oxygen production in mitochondria.

The objective of this study was to identify genes targeted by both copy number and copy-neutral changes in the right coronary arteries in the area of advanced atherosclerotic plaques and intact internal mammary arteries derived from the same individuals with comorbid coronary artery disease and metabolic syndrome. The artery samples from 10 patients were screened for genomic imbalances using array comparative genomic hybridization. Ninety high-confidence, identical copy number variations (CNVs) were detected. We also identified eight copy-neutral changes (cn-LOHs) > 1.5 Mb in paired arterial samples in 4 of 10 individuals. The frequencies of the two gains located in the 10q24.31 (ERLIN1) and 12q24.11 (UNG, ACACB) genomic regions were evaluated in 33 paired arteries and blood samples. Two patients contained the gain in 10q24.31 (ERLIN1) and one patient contained the gain in 12q24.11 (UNG, ACACB) that affected only the blood DNA. An additional two patients harboured these CNVs in both the arteries and blood. In conclusion, we discovered and confirmed a gain of the 10q24.31 (ERLIN1) and 12q24.11 (UNG, ACACB) genomic regions in patients with coronary artery disease and metabolic comorbidity. Analysis of DNA extracted from blood indicated a possible somatic origin for these CNVs.

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (∼16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (∼11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (∼8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

The distribution of the allele and genotype frequency for the TOMM40 gene polymorphic variants rs741780, rs157580, rs1160985, rs2075650, and rs8106922 was analyzed in a sampling of ethnic Russians from the city of Kemerovo. The study of the structure of linkage disequilibrium in terms of five studied polymorphic variants showed the presence ofa haplotype block 2 Kb in length, which includes three polymorphic variants, i.e., rs741780, rs1160985, and rs8106922. The differences in the frequencies of alleles and genotypes in terms of the polymorphic rs2075650 and rs157580 variants between ethnic Russians from the city of Kemerovo and other European populations were detected. It was discovered that polymorphic variants of TOMM40 rs741780, rs1160985, and rs8106922 are associated with serum triglyceride concentrations. In men, the polymorphic variant rs2075650 is associated with low-density lipoprotein cholesterol levels. In women, the polymorphic variant rs741780 is associated with diastolic blood pressure levels.

Life span depends on many factors, including the level of reactive oxygen species, like superoxide radical. Superoxide radical is produced from oxygen in the course of the oxidation of NADPH to NADP+. The process is catalyzed by NADPH oxidase. In this study, genotype and allele distributions of the C242T (rs4673) polymorphism in the CYBA gene, which encodes the α subunit of NADPH oxidase (p22phox), were examined in the sample of long livers and in the population sample of the city of Tomsk. Statistically significantly higher frequency of T allele among female long livers (34.625%), compared to the females from Russian population (26.32%) was demonstrated (χ2 = 5.226; p = 0.022; OR = 1.48). Thus, the T allele is associated with a high life expectancy in females from the Russian population. No such association was observed for males from the same population.

For identification of somatic mitochondrial DNA (mtDNA) mutations, the mtDNA major noncoding region (D-loop) sequence in blood samples and carotid atherosclerosis plaques from patients with atherosclerosis was analyzed. Five point heteroplasmic positions were observed in 4 of 23 individuals (17%). Only in two cases could heteroplasmy have resulted from somatic mutation, whereas three heteroplasmic positions were found in both vascular tissue and blood. In addition, length heteroplasmy in a polycytosine stretches was registered at nucleotide positions 303-315 in 16 individuals, and also in the 16184-16193 region--in four patients. The results suggest that somatic mtDNA mutations can occur during atherosclerosis, but some heteroplasmic mutations may appear in all tissues, possibly being inherited.

Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars—a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni- and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China.

In this study we genotyped polymorphism Thr12Ser (rs1937) in TFAM gene in two groups: patients with coronary artery disease and control group (people from Tomsk population). For genotyping was used restriction fragment length polymorphism. We have found significant higher genotype CC frequency in men with coronary artery disease — 4.52% compared with control men — 0.45% (χ2 = 6.315; р = 0.043; OR = 10.45). Thus genotype CC is associated with coronary artery disease in men fromTomsk population.

In this study, we genotyped polymorphism in GPX1 Pro198→Leu (C→T) rs 1050450 in four groups, i.e., patients with coronary artery disease, people who lived a long time (over 90 years), people who died early (before 55 years) from cardiovascular disease, and the Russian population as a control group. We have found a significant higher T-allele frequency in men with coronary artery disease, i.e., 34.84% (χ2 = 5.228, p = 0.022; OR =1.46), and in men who died early from cardiovascular diseases, 38.16% (χ2 = 6.461, p = 0.011; OR = 1.69) compared to men in the control group, 26.8%. Moreover, a significantly higher genotype TT frequency has been shown in patients with coronary artery disease and myocardial infarction before age 50, which is 19.44% compared to the control group, which was 7.28% (χ2 = 9.55, p = 0.002). The TT frequency in individuals who lived a long time (4.39%) was the lowest and differed significantly from the group with coronary artery disease, which was 12.79% (χ2 = 8.07, p = 0.0045), and from the subgroup with coronary artery disease with myocardial infarction before age 50, which was 19.44% (χ2 = 14.49, p = 0.0001). Thus, our results indicate that the TT allele (Leu) of GPX1 Pro198→Leu (C > T) polymorphism is unfavorable for successful aging; it leads to predisposition to coronary artery disease, early myocardial infarction (before age 50), and early death (before age 55).

Polymorphic markers were studied in mitochondrial DNA and the nuclear POLG1 gene, coding for mitochondrial DNA polymerase γ. Their frequencies were compared between healthy individuals and patients with arterial hypertension, as well as between patients with and without left ventricular hypertrophy. The healthy group was found not to be clearly dominated by the C allele of MspI polymorphism in POLG1. Mitochondrial haplogroup H was more frequent (OR = 0.42; 95%CI 0.17–0.98; p = 0.043) in patients without left ventricular hypertrophy than in patients having this complication. Haplogroup T was more often detected in patients with left ventricular hypertrophy (OR = 6.16; 95%CI 1.17–9.74; p = 0.018). This result suggests the implication of mitochondrial DNA in hereditary susceptibility to cardiovascular diseases.

A group of patients with ischemic heart disease and myocardial infarction (N = 156) and a reference population sample (N = 300) were genotyped for 58 single nucleotide polymorphisms (SNPs) in the genes involved in extracellular matrix function and collagen metabolism or associated with cardiovascular diseases and atherosclerotic plaque stability. Genotyping was performed by mass-spectrometry with two multiplex sets of 27 and 31 SNPs. The study revealed different genetic composition of predisposition to cardiovascular disease continuum (CVDC) syntropy (patients with concomitant conditions: hypercholesterolemia, hypertension, and type-II diabetes mellitus, N = 96) and to isolated myocardial infarction (without these conditions, N = 60). Only the KIAA1462 gene (rs3739998) showed associations with both CVDC syntropy (OR = 1.71; 95% CI 1.19-2.45; р = 0.003) and isolated infarction (OR = 1.58; 95% CI 1.05-2.40; р = 0.028). Isolated myocardial infarction was also associated with LIG1 (rs20579) (OR = 2.08; 95% CI 1.06-4.17; р = 0.028) and ADAMDEC1 (rs3765124) (OR = 1.63; 95% CI 1.07-2.50; р = 0.020). CVDC syntropy was associated with CDKN2BAS1 (rs1333049) (OR = 1.48; 95% CI 1.03-2.12; р = 0.029) and APOA2 (rs5082) (OR = 1.47; 95% CI 1.02-2.11; р = 0.035). So, genes involved in fibrogenesis contribute to predisposition to the myocardial infarction as well. Isolated myocardial infarction and CVDC syntropy can be considered as pathogenetically different cardiovascular conditions, with different genes that contribute to the susceptibility.

The distribution of the allele and genotype frequency for the TOMM40 gene polymorphic variants rs741780, rs157580, rs1160985, rs2075650, and rs8106922 was analyzed in a sampling of ethnic Russians from the city of Kemerovo. The study of the structure of linkage disequilibrium in terms of five studied polymorphic variants showed the presence ofa haplotype block 2 Kb in length, which includes three polymorphic variants, i.e., rs741780, rs1160985, and rs8106922. The differences in the frequencies of alleles and genotypes in terms of the polymorphic rs2075650 and rs157580 variants between ethnic Russians from the city of Kemerovo and other European populations were detected. It was discovered that polymorphic variants of TOMM40 rs741780, rs1160985, and rs8106922 are associated with serum triglyceride concentrations. In men, the polymorphic variant rs2075650 is associated with low-density lipoprotein cholesterol levels. In women, the polymorphic variant rs741780 is associated with diastolic blood pressure levels.

We have performed association analysis for mtDNA most common variants and haplogroups with myocardial infarction and some prognostic characteristics in patients. Comparison of patients (N=406) and controls (N=183) has shown higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p=0.033). Patients with early infarction (before age 55), comparing to patiens older than 55 and the first infarction, had higher frequency of 16189C variant (24.1 vs. 12.5%; p=0.008); also, haplogroup U2e was registered only in the subgroup with early infarction (4.4%; p=0.004). On the other side, haplogroup U5 was less frequent in the patients with early infarction (5.1% vs. 15.4%; p=0.002). The patients with recurring cardiovascular incidents during one year follow-up had higher frequency of haplogroup H1 (20% versus 4.5% in the patients without complications, p=0.002) and variant 16189C (30% versus 13.5%; p=0.018). Haplogroup U5 was more frequent in the group of patients with left ventricular ejection fraction less than 40%: 17.1% comparing to 8.2% in the group with ejection fraction40%; p=0.034. The results suggest that mtDNA polymorphism contributes to coronary atherosclerosis. The associations could be explained by the polymorphism effect on oxidative phosphorylation and reactive oxygen production in mitochondria.

The A2350G polymorphism of exon 17 of the angiotensin I-converting enzyme gene (ACE) and the A1166C polymorphism of the 3′-untranslated region (3′-UTR) of the angiotensin II type 1 receptor gene (AGTR1) were tested for association with left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) or arterial hypertension (AH) combined with diabetes mellitus type 2 (DM2). The patients with EH or AH + DM2 did not differ significantly in ACE or AGTR1 allele or genotype frequencies from healthy subjects. Both polymorphisms were associated with LVH in EH. AGTR1 allele 1166C was more frequent in patients with LVH than without (33.6 vs. 20.7%) and affected the left ventricular mass index (LVMI) in patients with EH (p = 0.007). The frequency of ACE allele 2350G in EH patients with LVH was 1.5 times higher, and that of genotype GG was 3.5 times higher, than in patients without LVH. LVMI differed significantly (p = 0.002) between patients with different ACE genotypes, being maximum in homozygotes GG and minimum in homozygotes AA. Thus, AGTR1 allele 1166C and ACE allele 2350G were identified as predisposing to LVH in EH. The two polymorphisms were not associated with the incidence or severity of LVH in patients with AH and DM2.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA haplogroup (Hg) H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian and Altaian populations. In addition to the seven previously specified sub-haplogroups, we define fifteen novel sub-clades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one sub-cluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1(*), H1b, H1f, H2a, H3, H6a, H6b and H8 demonstrate distinct phylogeographic patterns. The monophyletic sub-haplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

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.

A sample of 165 patients with myocardial infarction (MI) with ST segment elevation has been studied to construct a prediction model for one-year period complications (recurrent nonfatal IM or cardiac death). Polymorphic genetic markers (n = 32) with confirmed role in pathogenesis of cardiovascular disease were analyzed. The best model to stratify patients by risk of post-IM complications included variants rs4291 (A-240T) in the ACE gene, rs6025 (G1691A, Leiden mutation) in the F5, and rs5918 (Leu59Pro) in the IGTB3. C statistics for the genetic model was 0.75 (0.64; 0.86), p = 0.001, which is comparable with characteristics of the GRACE scale for the same patients' population: 0.73 (0.61; 0.85). Thereby, analysis of a limited number of genetic markers was sufficient to create risk prediction model for post-MI complications with comparable effectiveness to the model, which is currently in use in clinical practice. To confirm the clinical validity, the predictive model obtained in the study should be evaluated in independent samples of MI patients. Association analysis of individual genetic markers with patients' outcomes has revealed that T allele carrier status (AT and TT genotypes) rs4291 of the ACE and CG genotype rs328 of the LPL gene are risk factors for cardiac death during one year after MI; Leiden mutation (rs6025) of the F5 gene is related to the higher risk of recurrent non-fatal MI or death during one year; CC genotype of the rs10811661, located in 9p21 locus has a protective effect against recurrent MI or death within one year after acute event.

Variation of Mongoloid-specific restriction sites of mitochondrial genome was analyzed in three territorial groups of Tuvinians. Distribution of mitochondrial DNA haplogroups A, B, C, and D on the territory of the Tuva Republic was estimated. The populations studied did not display distinct differentiation in respect to the mtDNA polymorphism. The specific feature of Tuvinian mitochondrial gene pool was the prevalence of only one haplogroup C (over 40%), mainly represented by two mitotypes. The high frequency of this haplogroup makes Tuvinians similar to more northern Siberian populations. On the other hand, the presence of haplogroup B indicates that Tuvinians have affinity to ethnic groups of Central Asia.

Life span depends on many factors, including the level of reactive oxygen species, like superoxide radical. Superoxide radical is produced from oxygen in the course of the oxidation of NADPH to NADP+. The process is catalyzed by NADPH oxidase. In this study, genotype and allele distributions of the C242T polymorphism in the CYBA gene, which encodes the alpha subunit ofNADPH oxidase (p22phox), were examined in the sample of long livers and in the population sample of the city of Tomsk. Statistically significantly higher frequency of T allele among female long livers (34.62%), compared to the females from Russian population (26.32%) was demonstrated (chi2 = 5.226; p = 0.022; OR = 1.48). Thus, the T allele is associated with a high life expectancy in females from the Russian population. No such association was observed for males from the same population.

Study is devoted to "genes for mitochondria"--genes of mitochondrial genome and mitochondrial DNA polymerase gamma gene (POLG1). We compared frequencies of polymorphisms in mitochondrial DNA and in POLG1 between healthy individuals and patients with arterial hypertension, as well as between patients with and without left ventricular hypertrophy. We did not discover significant differences of distribution of C allele of MspI-polymorphism in POLG1 in studied group. We have shown higher prevalence of mitochondrial haplogroup H of mtDNA in patients without left ventricle hypertrophy (OR = 0.42; 95% CI 0.17-0.98; p = 0.043), while compared with patients having this complication. Haplogroup T was more frequently detected in patients with left ventricle hypertrophy (OR = 6.16; 95% CI 1.17-9.74; p = 0.018). This result suggest implication of mitochondrial DNA in hypertension-induced left venticular hypertrophy.

Contains fulltext : 81952.pdf (Publisher’s version ) (Closed access) The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.

Native Americans derive from a small number of Asian founders who likely arrived to the Americas via Beringia. However, additional details about the intial colonization of the Americas remain unclear. To investigate the pioneering phase in the Americas we analyzed a total of 623 complete mtDNAs from the Americas and Asia, including 20 new complete mtDNAs from the Americas and seven from Asia. This sequence data was used to direct high-resolution genotyping from 20 American and 26 Asian populations. Here we describe more genetic diversity within the founder population than was previously reported. The newly resolved phylogenetic structure suggests that ancestors of Native Americans paused when they reached Beringia, during which time New World founder lineages differentiated from their Asian sister-clades. This pause in movement was followed by a swift migration southward that distributed the founder types all the way to South America. The data also suggest more recent bi-directional gene flow between Siberia and the North American Arctic., La lista completa de autores que integran el documento puede consultarse en el archivo., Instituto Multidisciplinario de Biología Celular, Facultad de Ciencias Naturales y Museo

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.

Analysis of associations between idiopathic disturbances of cardiac conduction (DCC) and polymorphism of mitochondrial genome.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).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.Variability of mDNA may be an etiological factor of idiopathic DCC pathogenesis.

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.

Mitochondrial DNA region V deletion-insertion polymorphism was examined in three Tuvinian populations inhabiting western, northeastern, and southeastern parts of the republic. The 9-bp deletion was characterized by nonrandom distribution across the Tuva territory: its frequency in the western population (13.37%) was statistically significantly higher than that in the northeastern (4.62%), and southeastern populations, as well as in Mongols, who are territorially and ethnically close to Tuvinians. The insertion mutation in the region V was detected with a frequency of about 3% in two out of the three populations tested.

Mitochondrial DNA sequence variation was examined in three rural populations of the indigenous inhabitants from the Tuva Republic. The frequencies of restriction sites within the D-loop region of mtDNA were determined. The three populations studied demonstrated similar patterns of mtDNA polymorphism. Like other Siberian populations, Tuvinians were characterized by high frequencies of the HaeIII 16517 and AspS9I (Cfr13I) 16516 restriction sites (about 75%). Moreover, in Tuvinians, a relatively low (71 to 81%) frequency of the KpnI 16129 restriction site was observed. The frequency of the mitotype differing from the Cambridge sequence by the HaeIII 16517 and KpnI 16129 sites in Tuvinians was higher than in Mongols and Russians. The features of mtDNA polymorphism point to the similarity between Tuvinians and other Siberian ethnic groups (Sel'kups in particular). This can be explained by the contribution of the Samoyed component, along with the Turkic and Mongoloid ones, to the formation of the Tuvinian ethnic group.

Deletion-insertion polymorphism of the V region and restriction polymorphism of D-loop for seven restriction enzymes--AspS9I (Cfr3I isoschizomere), BamHI, Bme18I (AvaII), EcoRV, HaeIII, KpnI, and Kzo9I (Sau3AI)--in mitochondrial DNA (mt DNA) were studied in the indigenous population of southeastern Tuva Republic. The results were compared with the data on Russians, Mongols, Buryats, and Altaians. Tuvinians significantly differed from Mongols in the frequency of the 9-bp deletion of the V region (1.89 and 8.07%, respectively). Additionally, significant differences between Tuvinians and samples of Mongols and Russians were obtained for frequencies of the AspS9I, HaeIII, and KpnI restriction sites. A comparison of the polymorphism of mitochondrial genome in individuals of different sexes and ages was performed in the studied sample.

The paper discusses the main applications of achievements of mitochondrial genetics: human pathology (mitochondrial diseases, complex disease susceptibility genes) and population genetics (evolution of mankind, demographic history, and migration ways of populations). Awareness of the physiological properties of the well-known nucleotide sequences of mitochondrial DNA is ascertained to be a strategy for studying the functional organization of nuclear genome whose structure is all but completely decoded.