Genetic Structure of Susceptibility to Cardiovascular Continuum Comorbidity

Goncharova, I. A.; Koroleva, Yu. A.; Слепцов, А. А.; Pecherina, T. V.; Кашталап, В. В.; Puzyrev, V P; Nazarenko, M. S.

doi:10.1134/s1022795422100039

Cited by 2 publications

(3 citation statements)

References 49 publications

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“…In addition to the 27,578 CpG sites presented on the Illumina Infinium Human Methylation BeadChip 27k methyla tion array, the methylation status of fibrogenesis genes and DNA repair genes was analyzed separately. We chose genes associated with CHCV, liver fibrosis stages, the rate of fibrosis progression to liver cirrhosis and comorbid pathologies of CHCV, according to our previous studies (Goncharova et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…Our research team has been working on the genetic aspects of СHCV. As a result, we established the associations of polymorphisms in fibrogenesis genes and DNA repair genes with pathology and pathogenetically significant features, including stages of liver fibrosis (Goncharova et al, 2020). It is possible that there are features of the DNA methylation profile in liver tissue in the setting of fibrosis and cirrhosis induced by HCV and causing HCC.…”

Section: Introductionmentioning

confidence: 99%

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Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma

et al. 2023

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In this study we compared methylation levels of 27,578 CpG sites between paired samples of the tumor and surrounding liver tissues with various degrees of damage (fibrosis, cirrhosis) in HCV-induced hepatocellular carcinoma (HCC) patients, as well as between tumor and normal tissue in non-viral HCC patients, using GSE73003 and GSE37988 data from GEODataSets (https://www.ncbi.nlm.nih.gov/). A significantly lower number of differentially methylated sites (DMS) were found between HCC of non-viral etiology and normal liver tissue, as well as between HCC and fibrosis (32 and 40), than between HCC and cirrhosis (2450 and 2304, respectively, according to GSE73003 and GSE37988 datasets). As the pathological changes in the tissue surrounding the tumor progress, the ratio of hyper-/ hypomethylated DMSs in the tumor decreases. Thus, in tumor tissues compared with normal/fibrosis/cirrhosis of the liver, 75/62.5/47.7 % (GSE73003) and 16 % (GSE37988) of CpG sites are hypermethylated, respectively. Persistent hypermethylation of the ZNF154 and ZNF540 genes, as well as CCL20 hypomethylation, were registered in tumor tissue in relation to both liver fibrosis and liver cirrhosis. Protein products of the EDG4, CCL20, GPR109A, and GRM8 genes, whose CpG sites are characterized by changes in DNA methylation level in tumor tissue in the setting of cirrhosis and fibrosis, belong to “Signaling by G-protein-coupled receptors (GPCRs)” category. However, changes in the methylation level of the “driver” genes for oncopathology (АРС, CDKN2B, GSTP1, ELF4, TERT, WT1) are registered in tumor tissue in the setting of liver cirrhosis but not fibrosis. Among the genes hypermethylated in tumor tissue in the setting of liver cirrhosis, the most represented biological pathways are developmental processes, cell-cell signaling, transcription regulation, Wnt-protein binding. Genes hypomethylated in liver tumor tissue in the setting of liver cirrhosis are related to olfactory signal transduction, neuroactive ligand-receptor interaction, keratinization, immune response, inhibition of serine proteases, and zinc metabolism. The genes hypermethylated in the tumor are located at the 7p15.2 locus in the HOXA cluster region, and the hypomethylated CpG sites occupy extended regions of the genome in the gene clusters of olfactory receptors (11p15.4), keratin and keratin-associated proteins (12q13.13, 17q21.2, and 21q22.11), epidermal differentiation complex (1q21.3), and immune system function loci 9p21.3 (IFNA, IFNB1, IFNW1 cluster) and 19q13.41–19q13.42 (KLK, SIGLEC, LILR, KIR clusters). Among the genes of fibrogenesis or DNA repair, cg14143055 (ADAMDEC1) is located in the binding region of the HOX gene family transcription factors (TFs), while cg05921699 (CD79A), cg06196379 (TREM1) and cg10990993 (MLH1) are located in the binding region of the ZNF protein family transcription factor (TF). Thus, the DNA methylation profile in the liver in HCV-induced HCC is unique and differs depending on the degree of surrounding tissue lesion – liver fibrosis or liver cirrhosis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma

et al. 2023

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“…Генетические детерминанты ИМ недостаточно изучены, но с появлением полногеномных ассоциативных исследований (GWAS) выявлены участки генома, ассоциирование с риском развития ИМ и его неблагоприятного течения, включая летальный исход заболевания [7]. В своей основе ИМ имеет достаточно сложную генетическую структуру с разнообразными по частоте и эффектам комбинациями вариантов нуклеотидной последовательности (ВНП) и аллелей [8].…”

Section: Introductionunclassified

Cardiovascular risk personification: focus on the natriuretic peptide system

Hryachkova

Цепокина

Понасенко

2023

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A brief review presents current data on the possibilities of predicting the course of cardiovascular and other diseases, as well as the results of surgical treatment in patients by assessing the concentration of atrial, brain natriuretic peptides, polymorphic gene variants of these peptides and their receptors. Significant prospects for further research in this direction have been identified in order to develop prognostic molecular genetic panels for assessing the risk of developing myocardial infarction, arterial hypertension, heart failure in the framework of primary and secondary prevention.

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Genetic Structure of Susceptibility to Cardiovascular Continuum Comorbidity

Cited by 2 publications

References 49 publications

Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma

Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma

Cardiovascular risk personification: focus on the natriuretic peptide system

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