53 results on '"D. Ivanoshchuk"'
Search Results
2. A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2
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D. Ivanoshchuk, Alla Ovsyannikova, Andrey A. Yurchenko, Elena Shakhtshneider, Mikhail I. Voevoda, S. V. Mikhailova, Oksana D. Rymar, and V. I. Oblaukhova
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Proband ,010407 polymers ,genetic analysis ,QH426-470 ,Biology ,medicine.disease_cause ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Maturity onset diabetes of the young ,mody2 ,glucokinase gene ,maturity onset diabetes of the young ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Genetics ,medicine ,human ,Gene ,Genetic testing ,Mutation ,Splice site mutation ,medicine.diagnostic_test ,Glucokinase ,bioinformatics ,medicine.disease ,0104 chemical sciences ,030220 oncology & carcinogenesis ,next-generation sequencing ,General Agricultural and Biological Sciences - Abstract
The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic β-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580-1G>A substitution (IVS5 -1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro- and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method. Key words: human; maturity onset diabetes of the young; MODY2; glucokinase gene; next-generation sequencing; genetic analysis; bioinformatics.
- Published
- 2020
3. Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
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Olga Timoshchenko, Elena Shakhtshneider, Mikhail I. Voevoda, Andrew Goonko, D. Ivanoshchuk, Sergey Semaev, Emil S Valeev, P. S. Orlov, and Nataliya Ladygina
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APOC3 ,Proband ,Apolipoprotein B ,ABCG5 ,Medicine (miscellaneous) ,Familial hypercholesterolemia ,Article ,Exon ,medicine ,Multiplex ligation-dependent probe amplification ,LPL ,multiplex ligation-dependent probe amplification ,APOB ,Gene ,Genetics ,targeted sequencing technologies ,biology ,familial hypercholesterolemia ,rare variants ,nutritional and metabolic diseases ,Lipid metabolism ,SREBF1 ,medicine.disease ,Phenotype ,LDLR ,biology.protein ,Medicine ,lipids (amino acids, peptides, and proteins) - Abstract
The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the LDLR promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the LDLR gene were identified in 19 probands (73.1% of all variants identified in probands), in three probands (11.5%), pathogenic variants were found in the APOB gene, and in four probands (15.4%), rare, clinically significant variants were identified in genes LPL, SREBF1, APOC3, and ABCG5. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.
- Published
- 2021
4. Innate-Immunity Genes in Obesity
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S. V. Mikhailova and D. Ivanoshchuk
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obesity ,Innate immune system ,microbiome ,Medicine (miscellaneous) ,Adipokine ,Adipose tissue ,Review ,Biology ,Cell biology ,adipose tissue ,gene knockout ,polymorphism ,Crosstalk (biology) ,Immune system ,Lipotoxicity ,Medicine ,Microbiome ,innate immunity ,genetic predisposition ,Function (biology) - Abstract
The main functions of adipose tissue are thought to be storage and mobilization of the body’s energy reserves, active and passive thermoregulation, participation in the spatial organization of internal organs, protection of the body from lipotoxicity, and ectopic lipid deposition. After the discovery of adipokines, the endocrine function was added to the above list, and after the identification of crosstalk between adipocytes and immune cells, an immune function was suggested. Nonetheless, it turned out that the mechanisms underlying mutual regulatory relations of adipocytes, preadipocytes, immune cells, and their microenvironment are complex and redundant at many levels. One possible way to elucidate the picture of adipose-tissue regulation is to determine genetic variants correlating with obesity. In this review, we examine various aspects of adipose-tissue involvement in innate immune responses as well as variants of immune-response genes associated with obesity.
- Published
- 2021
5. Diagnostic the familial hypercholesterolemia in West Siberia using targeted high throughput sequencing
- Author
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E. Shakhtshneider, D. Ivanoshchuk, S. Semaev, O. Timoshchenko, and M. Voevoda
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Cardiology and Cardiovascular Medicine - Published
- 2022
6. Analysis of the variants of the F5 gene in men with coronary atherosclerosis
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A. M. Volkov, Elena Shakhtshneider, Y. Polonskaya, Vladimir N. Maksimov, D. Ivanoshchuk, A. Kurguzov, A. Chernyavsky, I. S. Murashov, E. Striukova, E. S. Valeev, Yuliya I. Ragino, and Elena V. Kashtanova
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medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Gene ,Coronary atherosclerosis - Published
- 2021
7. Next generation sequencing in sudden cardiac death (pilot study)
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I. A. Rodina, V. P. Novoselov, S. K. Malyutina, P. S. Orlov, Vladimir N. Maksimov, S. V. Maksimova, D. Ivanoshchuk, O. V. Khamovich, M I Voevoda, and A. A. Ivanova
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medicine.medical_specialty ,business.industry ,030204 cardiovascular system & hematology ,medicine.disease ,DNA sequencing ,sudden cardiac death ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,gene panel ,ngs ,Internal medicine ,RC666-701 ,molecular autopsy ,medicine ,Cardiology ,Diseases of the circulatory (Cardiovascular) system ,030216 legal & forensic medicine ,mutation ,Cardiology and Cardiovascular Medicine ,business ,exome - Abstract
Aim.To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.Materialandmethods.The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD:KCNQ1,KCNH2,SCN5A,AKAP9,ANK2,CACNA1C,CALM1,CALM2,CAV3,KCNE1,KNCJNE2,KCNE2,SCN4B,SNTA1,MYH2,APOB,KCNA5,TGFB3,NEB,PDX1,FLNC,PLEC,KCND3.Results.Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.Conclusion.This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.
- Published
- 2020
8. Analysis of APPL1 Gene Polymorphisms in Patients with a Phenotype of Maturity Onset Diabetes of the Young
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Yuliya I. Ragino, Elena Shakhtshneider, Mikhail I. Voevoda, S. V. Mikhailova, D. Ivanoshchuk, Oksana D. Rymar, P. S. Orlov, and Alla Ovsyannikova
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0301 basic medicine ,medicine.medical_specialty ,maturity onset diabetes of the young type 14 ,Population ,Medicine (miscellaneous) ,population ,lcsh:Medicine ,030209 endocrinology & metabolism ,Article ,Maturity onset diabetes of the young ,03 medical and health sciences ,0302 clinical medicine ,single-nucleotide variant ,Internal medicine ,Diabetes mellitus ,Genotype ,medicine ,APPL1 ,education ,Genetic association ,education.field_of_study ,Adiponectin ,business.industry ,lcsh:R ,Type 2 Diabetes Mellitus ,Odds ratio ,medicine.disease ,030104 developmental biology ,Endocrinology ,diabetes mellitus ,business - Abstract
The APPL1 gene encodes a protein mediating the cross-talk between adiponectin and insulin signaling. Recently, it was found that APPL1 mutations can cause maturity onset diabetes of the young, type 14. Here, an analysis of APPL1 was performed in patients with a maturity-onset diabetes of the young (MODY) phenotype, and prevalence of these mutations was estimated in a Russian population, among type 2 diabetes mellitus (T2DM) and MODY patients. Whole-exome sequencing or targeted sequencing was performed on 151 probands with a MODY phenotype, with subsequent association analysis of one of identified variants, rs11544593, in a white population of Western Siberia (276 control subjects and 169 T2DM patients). Thirteen variants were found in APPL1, three of which (rs79282761, rs138485817, and rs11544593) are located in exons. There were no statistically significant differences in the frequencies of rs11544593 alleles and genotypes between T2DM patients and the general population. In the MODY group, AG rs11544593 genotype carriers were significantly more frequent (AG vs. AA + GG: odds ratio 1.83, confidence interval 1.15&ndash, 2.90, p = 0.011) compared with the control group. An association of rs11544593 with blood glucose concentration was revealed in the MODY group. The genotyping data suggest that rs11544593 may contribute to carbohydrate metabolism disturbances.
- Published
- 2020
9. Association of RS708272 (CETP Gene Variant) with Lipid Profile Parameters and the Risk of Myocardial Infarction in the White Population of Western Siberia
- Author
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P. S. Orlov, Elena Shakhtshneider, Sergey Semaev, D. Ivanoshchuk, Mikhail I. Voevoda, Valery Gafarov, Sophia Malyutina, and Yuliya I. Ragino
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0301 basic medicine ,risk of cardiovascular disease ,white population ,medicine.medical_specialty ,TaqI ,rs708272 ,Population ,030204 cardiovascular system & hematology ,Biochemistry ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Medicine ,Risk factor ,Allele ,education ,Molecular Biology ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Western Siberia ,Odds ratio ,Confidence interval ,lipid profile ,030104 developmental biology ,chemistry ,Population study ,business ,Lipid profile - Abstract
The TaqI B (rs708272) single-nucleotide variant, i.e., the +279 G/A substitution in intron 1 of the CETP gene, is actively investigated as a risk factor of lipid metabolism disorders. The aim of this study was to analyze the association of rs708272 with lipid parameters and the risk of myocardial infarction in the population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >, 90% white, aged 45&ndash, 69 years, males: 50%). In total, 3132 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs708272 was analyzed by RT-PCR via TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays (Thermo Fisher Scientific, USA). The frequencies of rs708272 genotypes AA (homozygote), AG (heterozygote), and GG were 0.21, 0.49, and 0.30, respectively, in this population. Allele A frequency was 0.46. We found an association of allele G with low levels of high-density lipoprotein cholesterol and a high index of atherogenicity in this population (p <, 0.001 and p <, 0.001, respectively). Allele G was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval&thinsp, 1.208&ndash, 3.178, p = 0.008) and in the study population (odds ratio 1.465, 95% confidence interval 1.028&ndash, 2.087, p = 0.036). Thus, rs708272 is associated with myocardial infarction in the white population of Western Siberia (Russia).
- Published
- 2019
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10. Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia
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Oksana D. Rymar, Alla Ovsyannikova, Elena Shakhtshneider, D. Ivanoshchuk, S. V. Mikhailova, Yu. I. Ragino, Mikhail I. Voevoda, and P. S. Orlov
- Subjects
Male ,0301 basic medicine ,lcsh:Medicine ,Russia ,Gene Frequency ,Polymorphism (computer science) ,Coding region ,lcsh:QH301-705.5 ,Maturity onset diabetes of the young ,Single-nucleotide polymorphism ,Genetics ,rs149840771 ,education.field_of_study ,GLIS3 ,General Medicine ,Middle Aged ,DNA-Binding Proteins ,Research Note ,Carbohydrate Metabolism Disorder ,MODY ,Carbohydrate Metabolism ,Female ,Genotype ,Population ,Biology ,Polymorphism, Single Nucleotide ,White People ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Type 2 diabetes mellitus ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,lcsh:Science (General) ,Aged ,rs143051164 ,lcsh:R ,Type 2 Diabetes Mellitus ,rs806052 ,medicine.disease ,Repressor Proteins ,Minor allele frequency ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,lcsh:Biology (General) ,Trans-Activators ,Transcription Factors ,lcsh:Q1-390 - Abstract
Objective Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia. Results We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency
- Published
- 2018
11. A Case of Maturity Onset Diabetes of the Young (MODY3) in a Family with a Novel HNF1A Gene Mutation in Five Generations
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E. S. Malakhina, D. Ivanoshchuk, Alla Ovsyannikova, Elena Shakhtshneider, S. V. Mikhailova, Oksana D. Rymar, Mikhail I. Voevoda, and P. S. Orlov
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0301 basic medicine ,Proband ,Pediatrics ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Family history ,Case Report ,030209 endocrinology & metabolism ,Gene mutation ,HNF1A ,Maturity onset diabetes of the young ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Insulin ,HNF1A Gene Mutation ,MODY3 ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,030104 developmental biology ,Hyperglycemia ,business - Abstract
Diabetes mellitus with autosomal dominant inheritance, i.e., maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus. The MODY phenotype is associated with gene mutations leading to pancreatic β-cell dysfunction. Here, we present the clinical case of a 50-year-old proband with familial diabetes mellitus in five generations (proband, her mother, grandmother, great-grandfather, and son). This disease is most likely associated with the novel Ser6Arg mutation in the HNF1A gene, which was identified in four family members. The mutation was not detected in MODY patients (126 subjects), in patients with type 2 diabetes mellitus (188 subjects), and in a general population sample (564 subjects). Electronic supplementary material The online version of this article (10.1007/s13300-017-0350-8) contains supplementary material, which is available to authorized users.
- Published
- 2017
12. Between Lake Baikal and the Baltic Sea: genomic history of the gateway to Europe
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Ancha Baranova, V. P. Puzyrev, Tatiana V. Tatarinova, N. N. Trofimova, Vadim Stepanov, Marina Gubina, Rita Khusainova, A. V. Marusin, Egor Prokhortchouk, Edward J. Vajda, A. B. Teslyuk, Oleg Balanovsky, Eugenia S. Boulygina, Maria Spiridonova, I. M. Khidiyatova, Alexandr M. Mazur, Martin Triska, Irina Khitrinskaya, Svetlana V. Tsygankova, Natalia A Konovalova, Ganesh Prasad Arun Kumar, Ekaterina Khrameeva, Petr Triska, Nikolay Chekanov, Konstantin Babalyan, V. L. Akhmetova, Sergey Litvinov, Elza Khusnutdinova, Konstantin G. Skryabin, V. N. Kharkov, and D. Ivanoshchuk
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Male ,0301 basic medicine ,Genotyping Techniques ,Population genetics ,Datasets as Topic ,030105 genetics & heredity ,History, 18th Century ,Russia ,Ethnicity ,Slavic languages ,Khanty ,History, Ancient ,Genetics (clinical) ,History, 15th Century ,Genetics ,education.field_of_study ,History, 19th Century ,Emigration and Immigration ,Europe ,Biogeography ,History, 16th Century ,Genetic structure ,language ,Ethnology ,Female ,Algorithms ,Asia ,lcsh:QH426-470 ,Demographic history ,Old Believers ,Population ,IBD ,Eastern Europe ,Admixture ,Biology ,History, 21st Century ,History, 17th Century ,03 medical and health sciences ,Humans ,education ,Research ,Genetic Variation ,DNA ,History, 20th Century ,History, Medieval ,language.human_language ,Siberia ,lcsh:Genetics ,Genetics, Population ,030104 developmental biology - Abstract
Background The history of human populations occupying the plains and mountain ridges separating Europe from Asia has been eventful, as these natural obstacles were crossed westward by multiple waves of Turkic and Uralic-speaking migrants as well as eastward by Europeans. Unfortunately, the material records of history of this region are not dense enough to reconstruct details of population history. These considerations stimulate growing interest to obtain a genetic picture of the demographic history of migrations and admixture in Northern Eurasia. Results We genotyped and analyzed 1076 individuals from 30 populations with geographical coverage spanning from Baltic Sea to Baikal Lake. Our dense sampling allowed us to describe in detail the population structure, provide insight into genomic history of numerous European and Asian populations, and significantly increase quantity of genetic data available for modern populations in region of North Eurasia. Our study doubles the amount of genome-wide profiles available for this region. We detected unusually high amount of shared identical-by-descent (IBD) genomic segments between several Siberian populations, such as Khanty and Ket, providing evidence of genetic relatedness across vast geographic distances and between speakers of different language families. Additionally, we observed excessive IBD sharing between Khanty and Bashkir, a group of Turkic speakers from Southern Urals region. While adding some weight to the “Finno-Ugric” origin of Bashkir, our studies highlighted that the Bashkir genepool lacks the main “core”, being a multi-layered amalgamation of Turkic, Ugric, Finnish and Indo-European contributions, which points at intricacy of genetic interface between Turkic and Uralic populations. Comparison of the genetic structure of Siberian ethnicities and the geography of the region they inhabit point at existence of the “Great Siberian Vortex” directing genetic exchanges in populations across the Siberian part of Asia. Slavic speakers of Eastern Europe are, in general, very similar in their genetic composition. Ukrainians, Belarusians and Russians have almost identical proportions of Caucasus and Northern European components and have virtually no Asian influence. We capitalized on wide geographic span of our sampling to address intriguing question about the place of origin of Russian Starovers, an enigmatic Eastern Orthodox Old Believers religious group relocated to Siberia in seventeenth century. A comparative reAdmix analysis, complemented by IBD sharing, placed their roots in the region of the Northern European Plain, occupied by North Russians and Finno-Ugric Komi and Karelian people. Russians from Novosibirsk and Russian Starover exhibit ancestral proportions close to that of European Eastern Slavs, however, they also include between five to 10 % of Central Siberian ancestry, not present at this level in their European counterparts. Conclusions Our project has patched the hole in the genetic map of Eurasia: we demonstrated complexity of genetic structure of Northern Eurasians, existence of East-West and North-South genetic gradients, and assessed different inputs of ancient populations into modern populations. Electronic supplementary material The online version of this article (10.1186/s12863-017-0578-3) contains supplementary material, which is available to authorized users.
- Published
- 2017
13. Genetic analysis in Russian patients with familial hypercholesterolemia
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P. S. Orlov, D. Ivanoshchuk, Elena Shakhtshneider, and O. Timoshchenko
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Medicine ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Genetic analysis - Published
- 2021
14. Analysis of variants in the KLOTHO gene in patients with coronary atherosclerosis
- Author
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S. Semaev, Yuliya I. Ragino, Y. Nikitin, Elena Shakhtshneider, O. Timoshchenko, E.M. Stakhneva, and D. Ivanoshchuk
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Klotho ,Coronary atherosclerosis - Published
- 2021
15. Analysis of differential expression of the cytokine/chemokine genes in tissue of stable and unstable atherosclerotic plaques
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V. Fishman, Elena V. Kashtanova, D. Ivanoshchuk, Elena Shakhtshneider, Y. Polonskaya, A. Chernyavsky, I. S. Murashov, M I Voevoda, and Yuliya I. Ragino
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Chemokine ,Cytokine ,medicine.medical_treatment ,Cancer research ,medicine ,biology.protein ,Differential expression ,Biology ,Cardiology and Cardiovascular Medicine ,Gene - Published
- 2020
16. Molecular mechanisms of the interaction between the processes of the cell response to mechanical stress and neuronal apoptosis in primary open-angle glaucoma
- Author
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N. A. Konovalova, D. Ivanoshchuk, P. S. Demenkov, O. S. Konovalova, Inna N. Lavrik, Vladimir A. Ivanisenko, O. A. Podkolodnaya, Olga V. Saik, Nikita V. Ivanisenko, Timofey V. Ivanisenko, and N. A. Kolchanov
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0301 basic medicine ,genetic structures ,Open angle glaucoma ,Glaucoma ,Ocular hypertension ,Biology ,medicine.disease ,Bioinformatics ,eye diseases ,Human genetics ,Pathophysiology ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Retinal ganglion cell ,Genetics ,medicine ,Optic nerve ,Animal Science and Zoology ,sense organs ,Agronomy and Crop Science ,Gene - Abstract
Glaucoma is a chronic progressive disease. It involves more than 60 million people worldwide. Primary open-angle glaucoma (POAG) is one of its commonest forms. About 2.71 million people in the United States suffered from POAG in 2011. Currently, POAG is a major cause of irreversible vision loss. The risk of blindness in patients with treated open-angle glaucoma is 27%. It is known that the death of optic nerve cells can be triggered by mechanical stress caused by ocular hypertension, which induces neuronal apoptosis and occurs in patients with POAG. Many scientific publications are dedicated to proteins and genes involved in the development of POAG, including neuronal apoptosis and the cell response to mechanical stress (CRMS). However, the molecular mechanisms underlying the pathophysiology of POAG are still poorly understood. The reconstruction of associative networks describing the functional interactions between these genes/proteins, including biochemical reactions, regulatory interactions, and transport, requires automated knowledge extraction from scientific publications. This work aims to analyze the associative networks describing molecular interactions between proteins and genes involved in CRMS, neuronal apoptosis, and the development of POAG. It has been shown that genes associated with POAG are statistically significantly overrepresented among the genes involved in the interactions between CRMS and neuronal apoptosis in comparison to what is expected on a random basis. This finding may explain how POAG causes the death of the retinal ganglion cell.
- Published
- 2017
17. MODY in Siberia – molecular genetics and clinical characteristics
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Elena Shakhtshneider, Mikhail I. Voevoda, E. N. Voropaeva, Oksana D. Rymar, Alla Ovsyannikova, and D. Ivanoshchuk
- Subjects
medicine.medical_specialty ,RC620-627 ,mody ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Maturity onset diabetes of the young ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Clinical significance ,030212 general & internal medicine ,Family history ,genes ,Nutritional diseases. Deficiency diseases ,business.industry ,molecular genetic testing ,Diabetic retinopathy ,mutations ,medicine.disease ,diabetes mellitus ,Carbohydrate Metabolism Disorder ,business ,Dyslipidemia - Abstract
The diagnosis of maturity onset diabetes of the young (MODY) has high clinical significance in young patients (no absolute need for exogenous insulin; normoglycaemia in most patients achieved by dieting or taking oral hypoglycaemic agents) and their relatives (high probability of first-degree relatives being carriers of mutations, which requires a thorough collection of family history and determination of the parameters of carbohydrate metabolism). Aim. This study aimed was to determine the clinical characteristics of different subtypes of MODY in a Siberian region. Materials and Methods. We performed an examination, biochemical and hormonal blood tests, ultrasound and molecular genetic testing of 20 patients with a clinical diagnosis of MODY. Results. Four subtypes of MODY were verified: MODY2 in 11 patients, MODY3 in two, MODY8 in one and MODY12 in two. Eleven patients (69%) exhibited no clinical manifestations of carbohydrate metabolism disorders, and one patient showed weight loss during early stage of the disease. Comorbidities included dyslipidemia, thyroid gland disorders and arterial hypertension. One patient (6%) exhibited diabetic nephropathy; two (13%), diabetic retinopathy and three (19%), peripheral neuropathy of lower legs. All patients achieved the target carbohydrate metabolism; the level of C-peptide was within the reference range. Conclusion. Four different subtypes of MODY (2, 3, 8, 12) were diagnosed in the present study, which differed in their clinical characteristics, presence of complications and treatment strategies. Our knowledge of monogenic forms of diabetes is expanding with the development in molecular genetics, but several aspects related to them require further study.
- Published
- 2017
18. Analysis of Polymorphism rs1333049 (Located at 9P21.3) in the White Population of Western Siberia and Associations with Clinical and Biochemical Markers
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P. S. Orlov, Yuliya I. Ragino, Sofia Malyutina, D. Ivanoshchuk, Sergey Semaev, Elena Shakhtshneider, Valery Gafarov, and Mikhail I. Voevoda
- Subjects
Male ,0301 basic medicine ,risk of cardiovascular disease ,white population ,Genotype ,Population ,lcsh:QR1-502 ,Physiology ,030204 cardiovascular system & hematology ,Polymorphism, Single Nucleotide ,Biochemistry ,Article ,lcsh:Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Polymorphism (computer science) ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,Molecular Biology ,Alleles ,Aged ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Western Siberia ,Odds ratio ,Middle Aged ,Lipids ,Siberia ,lipid profile ,030104 developmental biology ,Chromosomal region ,Population study ,Female ,rs1333049 ,Lipid profile ,business ,Biomarkers - Abstract
The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters. The population included in the analyses was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >, 90% white, aged 45&ndash, 69, males: 50%). In total, 2729 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs1333049 was analyzed by RT-PCR (BioLabMix, Russia). Frequencies of rs1333049 genotypes C/C (homozygote), C/G (heterozygote), and G/G were 0.22, 0.51, and 0.27 in this population. The Allele G frequency was 0.53. We found an association of allele G with total cholesterol and low-density lipoprotein cholesterol levels among male participants (p = 0.004 and p = 0.002, respectively). Allele C was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval&thinsp, 1.14&ndash, 3.38, p = &thinsp, 0.017) and the study population (odds ratio 1.83, 95% confidence interval&thinsp, 1.23&ndash, 2.72, p&thinsp, =&thinsp, 0.004). Thus, rs1333049 is associated with myocardial infarction in the white population of Western Siberia (Russia).
- Published
- 2019
19. The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients
- Author
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Emil S Valeev, Elena Shakhtshneider, S. V. Mikhailova, Alla Ovsyannikova, Oksana D. Rymar, D. Ivanoshchuk, Mikhail I. Voevoda, Veniamin S. Fishman, and P. S. Orlov
- Subjects
0301 basic medicine ,HNF1B ,endocrine system ,Population ,population ,lcsh:Medicine ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,medicine.disease_cause ,Article ,HNF1A ,ABCC8 ,Maturity onset diabetes of the young ,maturity onset diabetes of the young ,03 medical and health sciences ,0302 clinical medicine ,single-nucleotide variant ,medicine ,Multiplex ligation-dependent probe amplification ,multiplex ligation-dependent probe amplification ,education ,Genetics ,Mutation ,education.field_of_study ,GCK ,biology ,lcsh:R ,medicine.disease ,HNF4A ,Phenotype ,030104 developmental biology ,MODY ,diabetes mellitus ,biology.protein ,next-generation sequencing - Abstract
Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-&beta, cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 &minus, 1G>, T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>, T, IVS3 c.713 +2 T>, A, and Arg238Lys in HNF1A.
- Published
- 2021
20. Polymorphism of the APPL1 gene in patients with carbohydrate metabolism disorders
- Author
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M I Voevoda, P. S. Orlov, V. Fishman, Alla Ovsyannikova, Elena Shakhtshneider, Yuliya I. Ragino, Oksana D. Rymar, D. Ivanoshchuk, and S. Mikhailova
- Subjects
APPL1 gene ,medicine.medical_specialty ,Endocrinology ,Polymorphism (materials science) ,Internal medicine ,Carbohydrate Metabolism Disorder ,medicine ,In patient ,Biology ,Cardiology and Cardiovascular Medicine - Published
- 2020
21. RNA-SEQ transcriptome analysis of stable and unstable atherosclerotic plaques
- Author
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I. S. Murashov, Elena V. Kashtanova, M I Voevoda, Elena Shakhtshneider, V. Fishman, Yuliya I. Ragino, Y. Polonskaya, D. Ivanoshchuk, and A. Chernyavsky
- Subjects
Transcriptome ,RNA-Seq ,Computational biology ,Biology ,Cardiology and Cardiovascular Medicine - Published
- 2020
22. Analysis of rare variants in genes related to aberrations of lipid metabolism in patients with coronary atherosclerosis
- Author
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M I Voevoda, V. Fishman, Elena Shakhtshneider, Y. Polonskaya, D. Ivanoshchuk, A. Chernyavsky, Yuliya I. Ragino, and Elena V. Kashtanova
- Subjects
business.industry ,Medicine ,Lipid metabolism ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Bioinformatics ,Gene ,Coronary atherosclerosis - Published
- 2020
23. Polymorphism of the USF1 gene and lipid profile in Russian population
- Author
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Elena Shakhtshneider, M I Voevoda, S. Semaev, Yuliya I. Ragino, and D. Ivanoshchuk
- Subjects
Genetics ,medicine.diagnostic_test ,biology ,Polymorphism (materials science) ,medicine ,USF1 ,biology.protein ,Russian population ,Cardiology and Cardiovascular Medicine ,Lipid profile ,Gene - Published
- 2020
24. Polymorphism of the c-fms, ITGB3, CCR2, and DBH genes in the populations of old believers of the Tyumen oblast and Russian residents of Novosibirsk
- Author
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Marina Gubina, O. O. Latieva, A. K. Shuryaeva, Vladimir N. Maksimov, I. G. Solov’eva, M. N. Ponomareva, Vladimir N. Babenko, Mikhail I. Voevoda, N. A. Konovalova, and D. Ivanoshchuk
- Subjects
0301 basic medicine ,Genetics ,030102 biochemistry & molecular biology ,Old Believers ,Biophysics ,virus diseases ,hemic and immune systems ,Biology ,Significant negative correlation ,Loss of heterozygosity ,03 medical and health sciences ,Structural Biology ,Polymorphism (computer science) ,Control sample ,Allele ,Indel ,Gene ,geographic locations - Abstract
Old Believers of the Tyumen oblast have been studied compared with a control sample of Russian residents of the city of Novosibirsk. The former are a unique subpopulation, which has been relatively isolated from the rest of Russians in central and northern regions of Russia due to religious reasons since the middle of the 17th century. Polymorphisms in the genes for glycoprotein ITGB3, dopamine-β-hydroxylase (DBH), and chemokine receptor CCR2 and two mutations in the c-fms gene have been analyzed. The populations are only similar in the c-fms indel. The frequencies of the rare alleles of CCR2, ITGB3, and 3'UTR of c-fms in the Old Believers are lower than in the sample of Novosibirsk Russians, and the rare allele of DBH is more frequent. A significant negative correlation is observed between DBH and CCR2 (r =–0.88; df = 4; P < 0.023). Apparently, these differences are related to the long-term isolation of Old Believers. This assumption is consistent with the fact that the levels of heterozygosity for most loci in Old Believers are lower than in Novosibirsk Russians.
- Published
- 2016
25. Molecular-genetic mechanisms of the interaction between processes of cell response to mechanical stress and neuronal apoptosis in primary open-angle glaucoma
- Author
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Inna N. Lavrik, P. S. Demenkov, O. S. Konovalova, N. A. Konovalova, D. Ivanoshchuk, Timofey V. Ivanisenko, N. A. Kolchanov, O. A. Podkolodnaya, Nikita V. Ivanisenko, V. A. Ivanisenko, and Olga V. Saik
- Subjects
neuronal apoptosis ,primary open-angle glaucoma ,Primary (chemistry) ,genetic structures ,Open angle glaucoma ,apoptosis ,cell response to mechanical stress ,poag ,QH426-470 ,Biology ,eye diseases ,associative gene networks ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,andsystem ,Genetics ,Cell response ,sense organs ,General Agricultural and Biological Sciences ,Neuronal apoptosis - Abstract
Glaucoma is a chronic and progressive disease, which affects more than 60 million people worldwide. Primary open-angle glaucoma (POAG) is one of the most common forms of glaucoma. For example, about 2.71 million people in the USA had primary open-angle glaucoma in 2011. Currently POAG is a major cause of irreversible vision loss. In patients with treated open-angle glaucoma the risk of blindness reached to be about 27 %. It is known that the death of optic nerve cells can be triggered by mechanical stress caused by increased intraocular pressure, which induces neuronal apoptosis and is observed in patients with POAG. Currently, there is a large number of scientific publications describing proteins and genes involved in the pathogenesis of POAG, including neuronal apoptosis and the cell response to mechanical stress. However, the molecular- genetic mechanisms underlying the pathophysiology of POAG are still poorly understood. Reconstruction of associative networks describing the functional interactions between these genes/proteins, including biochemical reactions, regulatory interactions, transport, etc., requires the use of methods of automated knowledge extraction from texts of scientific publications. The aim of the work was the analysis of associative networks, describing the molecular-genetic interactions between proteins and genes involved in cell response to mechanical stress (CRMS), neuronal apoptosis and pathogenesis of POAG using ANDSystem, our previous development for automated text analysis. It was shown that genes associated with POAG are statistically significantly more often represented among the genes involved in the interactions between CRMS and neuronal apoptosis than it was expected by random reasons, which can be an explanation for the effect of POAG leading to the retinal ganglion cell death.
- Published
- 2016
26. Полиморфизм геновc-fms, ITGB3, CCR2иDBHв популяциях староверов Тюмени и русских Новосибирска
- Author
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N. A. Konovalova, Marina Gubina, I. G. Solov’eva, M. N. Ponomareva, V. N. Maksimov, D. Ivanoshchuk, Vladimir N. Babenko, A. K. Shuryaeva, O. O. Latieva, and Mikhail I. Voevoda
- Subjects
General Medicine - Published
- 2016
27. MOESM1 of Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia
- Author
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E. Shakhtshneider, S. Mikhailova, D. Ivanoshchuk, P. Orlov, A. Ovsyannikova, O. Rymar, Yu. Ragino, and M. Voevoda
- Abstract
Additional file 1. Genetic analysis of rs806052, rs143051164, and rs149840771. Sequencing, RT-PCR conditions, and in silico analysis for the GLIS3 gene.
- Published
- 2018
- Full Text
- View/download PDF
28. Association of the genetic markers for myocardial infarction with sudden cardiac death
- Author
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Vladimir N. Maksimov, A. A. Ivanova, D. Ivanoshchuk, P. S. Orlov, Sergei V. Savchenko, and Mikhail I. Voevoda
- Subjects
Male ,0301 basic medicine ,Myocardial Infarction ,rs499818 ,Genome-wide association study ,030204 cardiovascular system & hematology ,Gastroenterology ,Russia ,Sudden cardiac death ,0302 clinical medicine ,Risk Factors ,Genotype ,Medicine ,Myocardial infarction ,rs4804611 ,Incidence ,Incidence (epidemiology) ,Middle Aged ,Protein-Tyrosine Kinases ,rs1376251 ,Survival Rate ,9p21 ,rs2549513 ,Cardiology ,Original Article ,Female ,Cardiology and Cardiovascular Medicine ,rs17465637 ,Genetic Markers ,medicine.medical_specialty ,RD1-811 ,Single-nucleotide polymorphism ,Real-Time Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Risk Assessment ,03 medical and health sciences ,Proto-Oncogene Proteins ,Internal medicine ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Genetic Predisposition to Disease ,Survival rate ,Retrospective Studies ,business.industry ,DNA ,medicine.disease ,Genotype frequency ,Death, Sudden, Cardiac ,030104 developmental biology ,RC666-701 ,rs619203 ,Surgery ,business ,Genome-Wide Association Study - Abstract
Objective: Investigate the association of rs17465637 gene MIAF3 (1q41), rs1376251 gene TAS2R50 (12p13), rs4804611 gene ZNF627 (19p13), rs619203 gene ROS1 (6q22), rs1333049 (9p21), rs10757278 (9p21), rs2549513 (16q23), rs499818 (6p24) associated with myocardial infarction available from the international genome-wide studies with sudden cardiac death (SCD) in a case–control study. Methods: A sample of SCD cases (n = 285) was formed using the WHO criteria; the control sample (n = 421) was selected according to sex and age. DNA was isolated by phenol–chloroform extraction from the myocardial tissue of SCD cases and blood of control cases. The groups were genotyped for the selected SNPs by real-time PCR using TaqMan probes (Applied Biosystems, United States). Results: No statistically significant differences in the genotype and allelic frequencies of studied single nucleotide polymorphisms between sudden cardiac death cases and control were detectable in general group. By separating the groups of sex and age differences in the genotype frequencies of rs1333049, rs10757278 and rs499818 are statistical significance. Genotypes CC of rs1333049 and GG of rs10757278 are associated with an increased sudden cardiac death risk in men (p = 0.019, OR = 1.7, 95% CI 1.1–2.8; p = 0.011, OR = 1.8, 95% CI 1.2–2.8, respectively). Genotype AG of rs499818 is associated with an increased sudden cardiac death risk in the women over 50 years old (p = 0.009, OR = 2.4, 95% CI 1.3–4.6). Conclusion: Polymorphisms rs1333049 and rs10757278 are associated with SCD in men and rs499818 in the women aged over 50 years.
- Published
- 2017
29. Analysis Of The Ldlr, Apob, Pcsk9 And Ldlrap1 Genes Variability In Patients With Familial Hypercholesterolemia In West Siberia Using Targeted High Throughput Resequencing
- Author
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M I Voevoda, D. Ivanoshchuk, Elena Shakhtshneider, O. Timoshchenko, and P. S. Orlov
- Subjects
Genetics ,Apolipoprotein B ,PCSK9 ,LDL receptor ,medicine ,biology.protein ,In patient ,Familial hypercholesterolemia ,Biology ,Cardiology and Cardiovascular Medicine ,medicine.disease ,Throughput (business) ,Gene - Published
- 2019
30. Rs1333049 And Lipid Profile In Russia Population
- Author
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M I Voevoda, D. Ivanoshchuk, Elena Shakhtshneider, S. K. Malyutina, Vladimir N. Maksimov, P. S. Orlov, S. Semaev, and Yuliya I. Ragino
- Subjects
education.field_of_study ,medicine.diagnostic_test ,Population ,medicine ,Food science ,Biology ,Cardiology and Cardiovascular Medicine ,education ,Lipid profile - Published
- 2019
31. Analysis Of Differential Expression Of Matrix Metalloproteinases Genes In Stable And Unstable Atherosclerotic Plaques
- Author
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V. Fishman, M I Voevoda, S. Mikhailova, A. Chernyavsky, Elena V. Kashtanova, Elena Shakhtshneider, Yuliya I. Ragino, Y. Polonskaya, D. Ivanoshchuk, and I. S. Murashov
- Subjects
Chemistry ,Differential expression ,Matrix metalloproteinase ,Cardiology and Cardiovascular Medicine ,Gene ,Cell biology - Published
- 2019
32. Hyperlipidemia In Patients With Mody2 And Mody3 In Russia
- Author
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Elena Shakhtshneider, M I Voevoda, D. Ivanoshchuk, S. Mikhailova, Alla Ovsyannikova, Yuliya I. Ragino, and Oksana D. Rymar
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Hyperlipidemia ,medicine ,In patient ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2019
33. Targeted Next-Generation Sequencing Of The Apoa5-A4-C3-A1 Gene Cluster In Patients With Diabetes Mellitus
- Author
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Elena Shakhtshneider, M I Voevoda, Oksana D. Rymar, Alla Ovsyannikova, D. Ivanoshchuk, and P. S. Orlov
- Subjects
business.industry ,Diabetes mellitus ,Gene cluster ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Bioinformatics ,DNA sequencing - Published
- 2019
34. Association of Polymorphism in SCN5A, GJA5, and KCNN3 Gene with Sudden Cardiac Death
- Author
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A. A. Ivanova, Mikhail I. Voevoda, D. Ivanoshchuk, V. P. Novoselov, S. V. Savchenko, P. S. Orlov, and Vladimir N. Maksimov
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Genotype ,Small-Conductance Calcium-Activated Potassium Channels ,Single-nucleotide polymorphism ,030204 cardiovascular system & hematology ,Gastroenterology ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Connexins ,Sudden cardiac death ,NAV1.5 Voltage-Gated Sodium Channel ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Gene ,Allele frequency ,Alleles ,business.industry ,Case-control study ,General Medicine ,Middle Aged ,medicine.disease ,Control subjects ,030104 developmental biology ,Death, Sudden, Cardiac ,Case-Control Studies ,Female ,business - Abstract
We studied association of single-nucleotide SCN5A (rs1805124), GJA5 (rs35594137), and KCNN3 (rs13376333) polymorphisms and sudden cardiac death. Humans died suddenly from cardiac causes (N=379) and unrelated sex- and age-matched control subjects were genotyped. No significant intergroup differences were found in the frequency of rs1805124 and rs13376333 genotypes and alleles. In women under 50 years, enhanced risk of sudden cardiac death was associated with rs35594137 GG genotype (OR=3.6; 95%CI=1.2-10.4; p=0.022), while in older women it was associated with rs35594137 AA genotype (OR=3.0; 95%CI=2.3-3.9; p=0.041). In women under 50 years, GA rs35594137 genotype was associated with a protective effect against sudden cardiac death (OR=0.3; 95%CI=0.1-0.8; p=0.036). Thus, GJA5 gene rs35594137 polymorphism is significantly associated with sudden cardiac death in the examined group.
- Published
- 2016
35. The spectrum of mutations in the CEL gene in early onset diabetes patients
- Author
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Alla Ovsyannikova, Oksana D. Rymar, Yulia Ragino, Elena Shakhtshneider, Mikhail I. Voevoda, Alexander Kurilshikov, and D. Ivanoshchuk
- Subjects
business.industry ,Diabetes mellitus ,Immunology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Gene ,Early onset - Published
- 2017
36. Association of polymorphism the APOE gene with cardiovascular risk factors and unfavorable long-term prognosis
- Author
-
M I Voevoda, Elena Shakhtshneider, L. V. Shcherbakova, S. K. Malyutina, D. Ivanoshchuk, P. S. Orlov, and Yuliya I. Ragino
- Subjects
Apolipoprotein E ,business.industry ,Cardiovascular risk factors ,Medicine ,Cardiology and Cardiovascular Medicine ,Bioinformatics ,business - Published
- 2018
37. Clinical case: The development of heterozygous familial hypercholesterolemia in a patient with rs879255191 in LDLR gene
- Author
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D. Ivanoshchuk, K. Makarenkova, S. Bazhan, M I Voevoda, O. Timoshchenko, P. S. Orlov, and Elena Shakhtshneider
- Subjects
business.industry ,Ldlr gene ,medicine ,Clinical case ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,Bioinformatics ,medicine.disease ,business - Published
- 2018
38. Targeted next-generation sequencing of the LDLRAP1 gene in patients with familial hypercholesterolemia
- Author
-
P. S. Orlov, Elena Shakhtshneider, K. Makarenkova, D. Ivanoshchuk, Yuliya I. Ragino, and M I Voevoda
- Subjects
business.industry ,medicine ,In patient ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,Bioinformatics ,medicine.disease ,business ,DNA sequencing ,LDLRAP1 gene - Published
- 2016
39. Analysis of the LDLR gene variability in patients with familial hypercholesterolemia in Russia using targeted high throughput resequencing
- Author
-
P. S. Orlov, Elena Shakhtshneider, D. Ivanoshchuk, Mikhail I. Voevoda, K. Makarenkova, and Yulia Ragino
- Subjects
0301 basic medicine ,Genetics ,03 medical and health sciences ,030104 developmental biology ,business.industry ,Ldlr gene ,Medicine ,In patient ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Throughput (business) - Published
- 2017
40. The R46L polymorphism of PCSK9 gene and lipid profile in Caucasian population of Russia
- Author
-
K. Astrakova, D. Ivanoshchuk, Yuliya I. Ragino, Elena Shakhtshneider, M I Voevoda, and S. Astrakov
- Subjects
Genetics ,PCSK9 Gene ,medicine.diagnostic_test ,medicine ,Biology ,Cardiology and Cardiovascular Medicine ,Lipid profile ,Caucasian population - Published
- 2016
41. Polymorphism in genes involved in lipid metabolism in MODY patients
- Author
-
A. Kurilshikov, D. Ivanoshchuk, Oksana D. Rymar, Yuliya I. Ragino, Elena Shakhtshneider, M I Voevoda, and Alla Ovsyannikova
- Subjects
Genetics ,Polymorphism (materials science) ,Lipid metabolism ,Biology ,Cardiology and Cardiovascular Medicine ,Gene - Published
- 2016
42. Cascade genetic screening for familial hypercholesterolemia in West Siberia
- Author
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M I Voevoda, Elena Shakhtshneider, Yuliya I. Ragino, D. Ivanoshchuk, P. S. Orlov, and K. Makarenkova
- Subjects
Genetics ,business.industry ,Medicine ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Published
- 2016
43. Diagnosis of Familial Hypercholesterolemia in Children and Young Adults.
- Author
-
Timoshchenko O, Ivanoshchuk D, Semaev S, Orlov P, Zorina V, and Shakhtshneider E
- Subjects
- Adolescent, Child, Humans, Young Adult, Adult, Middle Aged, Arteries, Lipids, Cardiovascular Diseases, Hyperlipoproteinemia Type II diagnosis, Hyperlipoproteinemia Type II epidemiology, Hyperlipoproteinemia Type II genetics, Atherosclerosis
- Abstract
The early detection and treatment of familial hypercholesterolemia (FH) in childhood and adolescence are critical for increasing life expectancy. The purpose of our study was to investigate blood lipid parameters, features of physical signs of cholesterol accumulation, and a personal and family history of premature cardiovascular diseases in children and young adults when FH is diagnosed. The analysis included patients under 18 years of age (n = 17) and young adults (18-44 years of age; n = 43) who received a diagnosis of FH according to clinical criteria. Targeted high-throughput sequencing was performed using a custom panel of 43 genes. A family history of cardiovascular diseases was more often noted in the group under 18 years of age than in young adults ( p < 0.001). Among young adults, there was a high prevalence of typical signs of the disease such as tendon xanthomas and the early development of arterial atherosclerosis ( p < 0.001). By molecular genetic testing, "pathogenic" and "probably pathogenic" variants were identified in the genes of 73.3% of patients under 18 years of age and 51.4% of patients 18-44 years of age. Thus, blood lipid screening tests combined with an accurate assessment of the family history is a highly relevant and inexpensive option for diagnosing FH in childhood. Molecular genetic testing allows us to make an accurate diagnosis and to improve adherence to treatment.
- Published
- 2023
- Full Text
- View/download PDF
44. Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity.
- Author
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Bairqdar A, Shakhtshneider E, Ivanoshchuk D, Mikhailova S, Kashtanova E, Shramko V, Polonskaya Y, and Ragino Y
- Abstract
The increase in the prevalence of overweight, obesity and associated diseases is a serious problem. The aim of the study was to identify rare variants in obesity-associated genes in young adults with abdominal obesity in our population and to analyze information about these variants in other populations. Targeted high-throughput sequencing of obesity-associated genes was performed (203 young adults with an abdominal obesity phenotype). In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ , FTO , GLP1R , GHRL , and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity.
- Published
- 2023
- Full Text
- View/download PDF
45. Association of Common Variants of APOE , CETP , and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study.
- Author
-
Semaev S, Shakhtshneider E, Shcherbakova L, Orlov P, Ivanoshchuk D, Malyutina S, Gafarov V, Voevoda M, and Ragino Y
- Subjects
- Male, Humans, Prospective Studies, Polymorphism, Single Nucleotide, Genotype, Alleles, Risk Factors, Apolipoproteins E genetics, Cholesterol Ester Transfer Proteins genetics, Genetic Predisposition to Disease, Myocardial Infarction genetics
- Abstract
The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.3, the CETP gene, and the APOE gene. In total, 2286 randomly selected patients were included. Rs708272 and rs429358 and rs7412 were analyzed using RT-PCR via the TaqMan principle, and rs1333049 vas analyzed via a commercial KASP assay. In our sample, the frequencies of alleles and genotypes were consistent with frequencies in comparable populations of Eastern and Western Europe. Allele C of rs1333049 was significantly associated with MI among males ( p = 0.027) and in the whole study sample ( p = 0.008). We also revealed a significant association of the ɛ2/ɛ4 genotype of APOE with MI among males ( p < 0.0001) and in the whole study sample ( p < 0.0001). Thus, among the tested polymorphisms, some genotypes of rs1333049 and rs429358 and rs7412 are the most strongly associated with MI and can be recommended for inclusion into a genetic risk score.
- Published
- 2023
- Full Text
- View/download PDF
46. Functionally Significant Variants in Genes Associated with Abdominal Obesity: A Review.
- Author
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Bairqdar A, Ivanoshchuk D, and Shakhtshneider E
- Abstract
The high prevalence of obesity and of its associated diseases is a major problem worldwide. Genetic predisposition and the influence of environmental factors contribute to the development of obesity. Changes in the structure and functional activity of genes encoding adipocytokines are involved in the predisposition to weight gain and obesity. In this review, variants in genes associated with adipocyte function are examined, as are variants in genes associated with metabolic aberrations and the accompanying disorders in visceral obesity.
- Published
- 2023
- Full Text
- View/download PDF
47. The Mutation Spectrum of Rare Variants in the Gene of Adenosine Triphosphate (ATP)-Binding Cassette Subfamily C Member 8 in Patients with a MODY Phenotype in Western Siberia.
- Author
-
Ivanoshchuk D, Shakhtshneider E, Mikhailova S, Ovsyannikova A, Rymar O, Valeeva E, Orlov P, and Voevoda M
- Abstract
During differential diagnosis of diabetes mellitus, the greatest difficulties are encountered with young patients because various types of diabetes can manifest themselves in this age group (type 1, type 2, and monogenic types of diabetes mellitus, including maturity-onset diabetes of the young (MODY)). The MODY phenotype is associated with gene mutations leading to pancreatic-β-cell dysfunction. Using next-generation sequencing technology, targeted sequencing of coding regions and adjacent splicing sites of MODY-associated genes ( HNF4A , GCK , HNF1A , PDX1 , HNF1B , NEUROD1 , KLF11 , CEL , PAX4 , INS , BLK , KCNJ11 , ABCC8 , and APPL1 ) was carried out in 285 probands. Previously reported missense variants c.970G>A (p.Val324Met) and c.1562G>A (p.Arg521Gln) in the ABCC8 gene were found once each in different probands. Variant c.1562G>A (p.Arg521Gln) in ABCC8 was detected in a compound heterozygous state with a pathogenic variant of the HNF1A gene in a diabetes patient and his mother. Novel frameshift mutation c.4609_4610insC (p.His1537ProfsTer22) in this gene was found in one patient. All these variants were detected in available family members of the patients and cosegregated with diabetes mellitus. Thus, next-generation sequencing of MODY-associated genes is an important step in the diagnosis of rare MODY subtypes.
- Published
- 2023
- Full Text
- View/download PDF
48. Associations of APOE Gene Variants rs429358 and rs7412 with Parameters of the Blood Lipid Profile and the Risk of Myocardial Infarction and Death in a White Population of Western Siberia.
- Author
-
Semaev S, Shakhtshneider E, Shcherbakova L, Ivanoshchuk D, Orlov P, Malyutina S, Gafarov V, Ragino Y, and Voevoda M
- Abstract
The present study aimed to analyze possible associations of rs7412 and rs429358 of the APOE gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 subjects, age 53.8 ± 7.0 years, males/females 50/50). PCR was conducted with fluorescence detection according to the TaqMan principle on a real-time PCR machine. The frequency of a minor allele (C) of rs429358 was 0.13, and the frequency of a minor allele (T) of rs7412 was 0.09. In our study, the woman with the rare ɛ1/ɛ4 genotype had substantial aberrations in blood lipid levels. In Kaplan-Meier curves, statistically significant differences were revealed in the prognosis of survival within the subgroup of females who had a myocardial infarction ( p = 0.0006): the prognosis was worse for carriers of the ɛ2/ɛ2 genotype and for ɛ4/ɛ4 carriers. Survival analysis regarding deaths from all causes showed ( p = 0.0238) that female carriers of the ɛ2/ɛ4 genotype had a worse prognosis than did carriers of other genotypes. Thus, in the population of Western Siberia (Russia), we confirmed statistically significant associations between rs7412 & rs429358 genotypes and lipid profile parameters.
- Published
- 2022
- Full Text
- View/download PDF
49. Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia).
- Author
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Shakhtshneider E, Ivanoshchuk D, Timoshchenko O, Orlov P, Semaev S, Valeev E, Goonko A, Ladygina N, and Voevoda M
- Abstract
The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the LDLR promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the LDLR gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the APOB gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes LPL , SREBF1 , APOC3 , and ABCG5 . In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.
- Published
- 2021
- Full Text
- View/download PDF
50. Genes Potentially Associated with Familial Hypercholesterolemia.
- Author
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Mikhailova S, Ivanoshchuk D, Timoshchenko O, and Shakhtshneider E
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 5 genetics, ATP Binding Cassette Transporter, Subfamily G, Member 8 genetics, Adaptor Proteins, Signal Transducing genetics, Animals, Cholesterol 7-alpha-Hydroxylase genetics, Genetic Predisposition to Disease, Humans, Lipase genetics, Lipoproteins genetics, Sterol Esterase genetics, Hyperlipoproteinemia Type II genetics
- Abstract
This review addresses the contribution of some genes to the phenotype of familial hypercholesterolemia. At present, it is known that the pathogenesis of this disease involves not only a pathological variant of low-density lipoprotein receptor and its ligands (apolipoprotein B, proprotein convertase subtilisin/kexin type 9 or low-density lipoprotein receptor adaptor protein 1), but also lipids, including sphingolipids, fatty acids, and sterols. The genetic cause of familial hypercholesterolemia is unknown in 20%-40% of the cases. The genes STAP1 (signal transducing adaptor family member 1), CYP7A1 (cytochrome P450 family 7 subfamily A member 1), LIPA (lipase A, lysosomal acid type), ABCG5 (ATP binding cassette subfamily G member 5), ABCG8 (ATP binding cassette subfamily G member 8), and PNPLA5 (patatin like phospholipase domain containing 5), which can cause aberrations of lipid metabolism, are being evaluated as new targets for the diagnosis and personalized management of familial hypercholesterolemia.
- Published
- 2019
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