Genomics of Stroke

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 55286

Special Issue Editors


E-Mail Website
Guest Editor
Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, 123182 Moscow, Russia
Interests: human genomics; pharmacogenomics; ischemic stroke; gene expression; non-coding RNAs
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Co-Guest Editor
Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, 123182 Moscow, Russia
Interests: functional genomics; ischemic stroke; next-generation sequencing; pharmacotranscriptomics; non-coding RNAs; microRNA; circular RNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stroke is a multifactorial disease and an extremely serious and socially important medical condition. The molecular genetic mechanisms for the pathogenesis and pharmacological correction of stroke remain largely unknown. However, the common use of high-throughput technologies, including genome-wide association studies (GWAS), DNA and RNA sequencing, and the development and analysis of model systems, has revealed genomic data suspected to be involved in predicting the risk and improving the diagnostics and treatment of stroke. Therefore, systematizing and discussing the results and prospects of stroke genomics is necessary.

This Special Issue entitled “Genomics of Stroke” is intended to provide a platform for a wide range of reviews, research articles, communications, and technical notes related to genetics studies of the pathogenesis, progression, diagnosis, and treatment of stroke. We encourage submissions that focus on a strong genomics component and are devoted to GWAS, functional studies of stroke-related genes or noncoding RNAs, model systems, pharmacogenomic and pharmacotranscriptomic studies, gene expression analyses, machine learning of the genetic markers associated with stroke, and other bioinformatics analyses of stroke using DNA or RNA sequencing data. Please contact the Guest Editors should you have any questions related to the scope of this Special Issue.

Prof. Dr. Svetlana A. Limborska
Dr. Ivan B. Filippenkov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stroke
  • genomics
  • pharmacogenomics
  • genetic markers of stroke
  • gene expression analyses
  • model systems of stroke

Published Papers (21 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 201 KiB  
Editorial
Special Issue “Genomics of Stroke” 2022
by Svetlana A. Limborska and Ivan B. Filippenkov
Genes 2023, 14(2), 514; https://doi.org/10.3390/genes14020514 - 17 Feb 2023
Viewed by 1067
Abstract
Stroke is one of the greatest medical threats to human health and quality of life in modern society [...] Full article
(This article belongs to the Special Issue Genomics of Stroke)
5 pages, 206 KiB  
Editorial
Special Issue: “Genomics of Stroke”
by Svetlana A. Limborska and Ivan B. Filippenkov
Genes 2022, 13(3), 415; https://doi.org/10.3390/genes13030415 - 25 Feb 2022
Cited by 1 | Viewed by 1426
Abstract
Stroke is a multifactorial disease and an extremely serious and socially important medical condition [...] Full article
(This article belongs to the Special Issue Genomics of Stroke)

Research

Jump to: Editorial, Review

19 pages, 6561 KiB  
Article
Temporal and Spatial Gene Expression Profile of Stroke Recovery Genes in Mice
by Jan Götz, Frederique Wieters, Veronika J. Fritz, Olivia Käsgen, Aref Kalantari, Gereon R. Fink and Markus Aswendt
Genes 2023, 14(2), 454; https://doi.org/10.3390/genes14020454 - 9 Feb 2023
Cited by 2 | Viewed by 2180
Abstract
Stroke patients show some degree of spontaneous functional recovery, but this is not sufficient to prevent long-term disability. One promising approach is to characterize the dynamics of stroke recovery genes in the lesion and distant areas. We induced sensorimotor cortex lesions in adult [...] Read more.
Stroke patients show some degree of spontaneous functional recovery, but this is not sufficient to prevent long-term disability. One promising approach is to characterize the dynamics of stroke recovery genes in the lesion and distant areas. We induced sensorimotor cortex lesions in adult C57BL/6J mice using photothrombosis and performed qPCR on selected brain areas at 14, 28, and 56 days post-stroke (P14-56). Based on the grid walk and rotating beam test, the mice were classified into two groups. The expression of cAMP pathway genes Adora2a, Pde10a, and Drd2, was higher in poor- compared to well-recovered mice in contralesional primary motor cortex (cl-MOp) at P14&56 and cl-thalamus (cl-TH), but lower in cl-striatum (cl-Str) at P14 and cl-primary somatosensory cortex (cl-SSp) at P28. Plasticity and axonal sprouting genes, Lingo1 and BDNF, were decreased in cl-MOp at P14 and cl-Str at P28 and increased in cl-SSp at P28 and cl-Str at P14, respectively. In the cl-TH, Lingo1 was increased, and BDNF decreased at P14. Atrx, also involved in axonal sprouting, was only increased in poor-recovered mice in cl-MOp at P28. The results underline the gene expression dynamics and spatial variability and challenge existing theories of restricted neural plasticity. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

15 pages, 2365 KiB  
Article
Insight into Glyproline Peptides’ Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia–Reperfusion
by Vasily V. Stavchansky, Ivan B. Filippenkov, Julia A. Remizova, Alina E. Denisova, Ivan V. Mozgovoy, Leonid V. Gubsky, Nikolay F. Myasoedov, Lyudmila A. Andreeva, Svetlana A. Limborska and Lyudmila V. Dergunova
Genes 2022, 13(12), 2380; https://doi.org/10.3390/genes13122380 - 16 Dec 2022
Cited by 3 | Viewed by 1721
Abstract
Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which [...] Read more.
Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which includes Met-Glu-His-Phe (MEHF) fragments of adrenocorticotropic hormone and the C-terminal tripeptide PGP, serves as a neuroprotective drug for the treatment of ischemic stroke. Previously, we revealed that Semax mostly prevented the disruption of the gene expression pattern 24 h after a transient middle cerebral artery occlusion (tMCAO) in a rat brain model. The genes of this pattern were grouped into an inflammatory cluster (IC) and a neurotransmitter cluster (NC). Here, using real-time RT-PCR, the effect of other PGP-containing peptides, PGP and Pro-Gly-Pro-Leu (PGPL), on the expression of a number of genes in the IC and NC was studied 24 h after tMCAO. Both the PGP and PGPL peptides showed Semax-unlike effects, predominantly without changing gene expression 24 h after tMCAO. Moreover, there were IC genes (iL1b, iL6, and Socs3) for PGP, as well as IC (iL6, Ccl3, Socs3, and Fos) and NC genes (Cplx2, Neurod6, and Ptk2b) for PGPL, that significantly changed in expression levels after peptide administration compared to Semax treatment under tMCAO conditions. Furthermore, gene enrichment analysis was carried out, and a regulatory gene network was constructed. Thus, the spectra of the common and unique effects of the PGP, PGPL, and Semax peptides under ischemia–reperfusion were distinguished. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

13 pages, 3127 KiB  
Article
Proteomic Markers in the Muscles and Brain of Pigs Recovered from Hemorrhagic Stroke
by Liliya Fedulova, Ekaterina Vasilevskaya, Olga Tikhonova, Laura Kazieva, Galina Tolmacheva and Alexandr Makarenko
Genes 2022, 13(12), 2204; https://doi.org/10.3390/genes13122204 - 24 Nov 2022
Cited by 3 | Viewed by 1548
Abstract
(1) Background: Stroke is the leading cause of serious long-term disability. Walking dysfunction and paresis of the upper extremities occurs in more than 80% of people who have had a stroke. (2) Methods: We studied post-genomic markers in biosamples of muscle and brain [...] Read more.
(1) Background: Stroke is the leading cause of serious long-term disability. Walking dysfunction and paresis of the upper extremities occurs in more than 80% of people who have had a stroke. (2) Methods: We studied post-genomic markers in biosamples of muscle and brain tissue from animals that underwent intracerebral hematoma and recovered after 42 days. Our purpose was to understand the biological mechanisms associated with recovery from hemorrhagic stroke. We analyzed the peptides formed after trypsinolysis of samples by HPLC-MS, and the results were processed by bioinformatics methods, including the establishment of biochemical relationships (gene to gene) using topological omics databases such as Reactome and KEGG. (3) Results: In the pig brain, unique compounds were identified which are expressed during the recovery period after traumatic injury. These are molecular factors of activated microglia, and they contribute to the functional recovery of neurons and reduce instances of hematoma, edema, and oxidative stress. Complexes of the main binding factors of the neurotrophins involved in the differentiation and survival of nerve cells were found in muscles. (4) Conclusions: A network of gene interactions has been constructed for proteins involved in the regulation of synaptic transmission, in particular presynaptic vesicular and endocytic processes. The presence of transmitters and transporters associated with stimulation of NMDA receptors at neuromuscular junctions shows the relationship between upper motor neurons and neuromuscular junctions. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

11 pages, 3427 KiB  
Article
Expression of Transcription Factor ZBTB20 in the Adult Primate Neurogenic Niche under Physiological Conditions or after Ischemia
by Dimo S. Stoyanov, Martin N. Ivanov, Tetsumori Yamashima and Anton B. Tonchev
Genes 2022, 13(9), 1559; https://doi.org/10.3390/genes13091559 - 29 Aug 2022
Cited by 3 | Viewed by 2313
Abstract
The Zbtb20 gene encodes for a transcription factor that plays an important role in mammalian cortical development. Recently, its expression was reported in the adult mouse subventricular zone (SVZ), a major neurogenic niche containing neural stem cells throughout life. Here, we analyzed its [...] Read more.
The Zbtb20 gene encodes for a transcription factor that plays an important role in mammalian cortical development. Recently, its expression was reported in the adult mouse subventricular zone (SVZ), a major neurogenic niche containing neural stem cells throughout life. Here, we analyzed its expression in the adult primate anterior SVZ (SVZa) and rostral migratory stream (RMS) using macaque monkeys (Macaca fuscata). We report that the majority of Ki67+ cells, 71.4% in the SVZa and 85.7% in the RMS, co-label for ZBTB20. Nearly all neuroblasts, identified by their Doublecortin expression, were positive for ZBTB20 in both regions. Nearly all GFAP+ neural stem cells/astrocytes were also positive for ZBTB20. Analysis of images derived from a public database of gene expression in control/ischemic monkey SVZa, showed evidence for ZBTB20 upregulation in postischemic monkey SVZa. Furthermore, the co-localization of ZBTB20 with Doublecortin and Ki67 was increased in the postischemic SVZa. Our results suggest that ZBTB20 expression is evolutionarily conserved in the mammalian neurogenic niche and is reactive to ischemia. This opens the possibility for further functional studies on the role of this transcription factor in neurogenesis in primates. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

18 pages, 5715 KiB  
Article
Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core
by Giulia Amico, Wayne O. Hemphill, Mariasavina Severino, Claudio Moratti, Rosario Pascarella, Marta Bertamino, Flavia Napoli, Stefano Volpi, Francesca Rosamilia, Sara Signa, Fred Perrino, Marialuisa Zedde, Isabella Ceccherini and on behalf of the Gaslini Stroke Study Group
Genes 2022, 13(7), 1179; https://doi.org/10.3390/genes13071179 - 30 Jun 2022
Cited by 2 | Viewed by 2402
Abstract
The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi–Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small [...] Read more.
The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi–Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.A136V and p.R174G TREX1 variants, respectively. Genetic findings, obtained by a customized panel including 183 genes associated with monogenic stroke, were combined with interferon signature testing and biochemical assays to determine the mutations’ effects in vitro. Our results for the p.A136V variant are inconsistent with prior biochemistry-pathology correlates for dominant AGS-causing TREX1 mutants. The p.R174G variant modestly altered exonuclease activity in a manner consistent with perturbation of substrate interaction rather than catalysis, which represents the first robust enzymological data for a TREX1 variant identified in a CADASIL-like patient. In conclusion, functional analysis allowed us to interpret the impact of TREX1 variants on patients’ phenotypes. While the p.A136V variant is unlikely to be causative for AGS in Patient A, Patient B’s phenotype is potentially related to the p.R174G variant. Therefore, further functional investigations of TREX1 variants found in CADASIL-like patients are warranted to determine any causal link and interrogate the molecular disease mechanism(s). Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

18 pages, 2524 KiB  
Article
Transcriptome Analysis Reveals Altered Expression of Genes Involved in Hypoxia, Inflammation and Immune Regulation in Pdcd10-Depleted Mouse Endothelial Cells
by Carmela Fusco, Grazia Nardella, Lucio Di Filippo, Elisabetta Dejana, Davide Cacchiarelli, Antonio Petracca, Lucia Micale, Matteo Malinverno and Marco Castori
Genes 2022, 13(6), 961; https://doi.org/10.3390/genes13060961 - 27 May 2022
Cited by 6 | Viewed by 2610
Abstract
Cerebral cavernous malformations (CCM) are capillary malformations affecting the central nervous system and commonly present with headaches, epilepsy and stroke. Treatment of CCM is symptomatic, and its prevention is limited. CCM are often sporadic but sometimes may be multifocal and/or affect multiple family [...] Read more.
Cerebral cavernous malformations (CCM) are capillary malformations affecting the central nervous system and commonly present with headaches, epilepsy and stroke. Treatment of CCM is symptomatic, and its prevention is limited. CCM are often sporadic but sometimes may be multifocal and/or affect multiple family members. Heterozygous pathogenic variants in PDCD10 cause the rarest and apparently most severe genetic variant of familial CCM. We carried out an RNA-Seq and a Q-PCR validation analysis in Pdcd10-silenced and wild-type mouse endothelial cells in order to better elucidate CCM molecular pathogenesis. Ninety-four differentially expressed genes presented an FDR-corrected p-value < 0.05. A functionally clustered dendrogram showed that differentially expressed genes cluster in cell proliferation, oxidative stress, vascular processes and immune response gene-ontology functions. Among differentially expressed genes, the major cluster fell in signaling related to inflammation and pathogen recognition, including HIF1α and Nos2 signaling and immune regulation. Validation analysis performed on wild-type, Pdcd10-null and Pdcd10-null reconstituted cell lines was consistent with RNA-Seq data. This work confirmed previous mouse transcriptomic data in endothelial cells, which are recognized as a critical tissue for CCM formation and expands the potential molecular signatures of PDCD10-related familial CCM to alterations in inflammation and pathogen recognition pathways. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

11 pages, 266 KiB  
Article
Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study
by Andrey V. Khrunin, Gennady V. Khvorykh, Alexandra V. Rozhkova, Evgeniya A. Koltsova, Elizaveta A. Petrova, Ekaterina I. Kimelfeld and Svetlana A. Limborska
Genes 2021, 12(12), 1938; https://doi.org/10.3390/genes12121938 - 30 Nov 2021
Cited by 2 | Viewed by 2085
Abstract
Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, [...] Read more.
Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, analysis of the results obtained from animal models of brain ischemia could be helpful. We have developed a bioinformatic approach exploring single nucleotide polymorphisms (SNPs) in human orthologues of rat genes expressed differentially under conditions of induced brain ischemia. Using this approach, we identified and analyzed nine SNPs in 553 Russian individuals (331 patients with IS and 222 controls). We explored the association of SNPs with both IS outcomes and with the risk of IS. SNP rs66782529 (LGALS3) was associated with negative IS outcomes (p = 0.048). SNPs rs62278647 and rs2316710 (PTX3) were associated significantly with IS (p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the PTX3 polymorphism. Thus, this research not only reveals some new genetic associations with IS and its outcomes but also shows how exploring variations in genes from a rat model of brain ischemia can be of use in searching for human genetic markers of this disorder. Full article
(This article belongs to the Special Issue Genomics of Stroke)
19 pages, 4760 KiB  
Article
Genome-Wide RNA-Sequencing Reveals Massive Circular RNA Expression Changes of the Neurotransmission Genes in the Rat Brain after Ischemia–Reperfusion
by Ivan B. Filippenkov, Vasily V. Stavchansky, Alina E. Denisova, Liya V. Valieva, Julia A. Remizova, Ivan V. Mozgovoy, Elizaveta I. Zaytceva, Leonid V. Gubsky, Svetlana A. Limborska and Lyudmila V. Dergunova
Genes 2021, 12(12), 1870; https://doi.org/10.3390/genes12121870 - 24 Nov 2021
Cited by 9 | Viewed by 2819
Abstract
Ischemic brain stroke is one of the most serious and socially significant diseases. In addition to messenger RNAs (mRNAs), encoding protein, the study of regulatory RNAs in ischemic has exceptional importance for the development of new strategies for neuroprotection. Circular RNAs (circRNAs) have [...] Read more.
Ischemic brain stroke is one of the most serious and socially significant diseases. In addition to messenger RNAs (mRNAs), encoding protein, the study of regulatory RNAs in ischemic has exceptional importance for the development of new strategies for neuroprotection. Circular RNAs (circRNAs) have a closed structure, predominantly brain-specific expression, and remain highly promising targets of research. They can interact with microRNAs (miRNAs), diminish their activity and thereby inhibit miRNA-mediated repression of mRNA. Genome-wide RNA-Seq analysis of the subcortical structures of the rat brain containing an ischemic damage focus and penumbra area revealed 395 circRNAs changed their expression significantly at 24 h after transient middle cerebral artery occlusion model (tMCAO) conditions. Furthermore, functional annotation revealed their association with neuroactive signaling pathways. It was found that about a third of the differentially expressed circRNAs (DECs) originate from genes whose mRNA levels also changed at 24 h after tMCAO. The other DECs originate from genes encoding non-regulated mRNAs under tMCAO conditions. In addition, bioinformatic analysis predicted a circRNA–miRNA–mRNA network which was associated with the neurotransmission signaling regulation. Our results show that such circRNAs can persist as potential miRNA sponges for the protection of mRNAs of neurotransmitter genes. The results expanded our views about the neurotransmission regulation in the rat brain after ischemia–reperfusion with circRNA action. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

18 pages, 7653 KiB  
Article
MicroRNA Analysis of Human Stroke Brain Tissue Resected during Decompressive Craniectomy/Stroke-Ectomy Surgery
by Andrew P. Carlson, William McKay, Jeremy S. Edwards, Radha Swaminathan, Karen S. SantaCruz, Ron L. Mims, Howard Yonas and Tamara Roitbak
Genes 2021, 12(12), 1860; https://doi.org/10.3390/genes12121860 - 23 Nov 2021
Cited by 10 | Viewed by 2562
Abstract
Background: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first [...] Read more.
Background: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue. Methods: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis. Results: miRNA NGS analysis detected 34 miRNAs with significantly aberrant expression in stroke tissue, as compared to non-stroke samples. Of these miRNAs, 19 were previously identified in stroke patient blood and CSF, while dysregulation of 15 miRNAs was newly detected in this study. miRNA direct target gene analysis and bioinformatics approach demonstrated a strong association of the identified miRNAs with stroke-related biological processes and signaling pathways. Conclusions: Dysregulated miRNAs detected in our study could be regarded as potential candidates for biomarkers and/or targets for therapeutic intervention. The results described herein further our understanding of the molecular basis of stroke and provide valuable information for the future functional studies in the experimental models of stroke. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

10 pages, 2055 KiB  
Article
Association of CYP26C1 Promoter Hypomethylation with Small Vessel Occlusion in Korean Subjects
by Eun-Ji Lee, Myung-Sunny Kim, Nam-Hui Yim and Min Ho Cha
Genes 2021, 12(10), 1622; https://doi.org/10.3390/genes12101622 - 14 Oct 2021
Cited by 1 | Viewed by 1802
Abstract
The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P450 family 26 subfamily C member 1 [...] Read more.
The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P450 family 26 subfamily C member 1 (CYP26C1) has not been identified. In this study, we measured the level of DNA methylation in the CYP26C1 promoter and the 5′ untranslated region of 115 normal subjects and 56 patients with SVO in Korea. The DNA methylation level of each subject was measured by bisulfite amplicon sequencing, and statistical analysis was performed using the general linear model or Pearson’s correlation. The average level of DNA methylation was markedly lower in patients with SVO than in normal subjects (20.4% vs. 17.5%). We found that the methylation of CYP26C1 has a significant positive correlation with blood parameters including white blood cells, hematocrit, lactate dehydrogenase, and Na+ in subjects with SVO. We predicted that binding of RXR-α and RAR-β might be affected by CYP26C1 methylation at CpG sites −246–237 and −294–285. These findings suggest that CYP26C1 methylation in the promoter region may be a predictor of SVO. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

10 pages, 718 KiB  
Article
Influence of Renal Impairment and Genetic Subtypes on Warfarin Control in Japanese Patients
by Tomotaka Tanaka, Masafumi Ihara, Kazuki Fukuma, Haruko Yamamoto, Kazuo Washida, Shunsuke Kimura, Akiko Kada, Shigeki Miyata, Toshiyuki Miyata and Kazuyuki Nagatsuka
Genes 2021, 12(10), 1537; https://doi.org/10.3390/genes12101537 - 28 Sep 2021
Cited by 2 | Viewed by 2048
Abstract
The genotypes of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) can influence therapeutic warfarin doses. Conversely, nongenetic factors, especially renal function, are associated with warfarin maintenance doses; however, the optimal algorithm for considering genes [...] Read more.
The genotypes of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) can influence therapeutic warfarin doses. Conversely, nongenetic factors, especially renal function, are associated with warfarin maintenance doses; however, the optimal algorithm for considering genes and renal dysfunction has not been established. This single-center prospective cohort study aimed to evaluate the factors affecting warfarin maintenance doses and develop pharmacogenetics-guided algorithms, including the factors of renal impairment and others. To commence, 176 outpatients who were prescribed warfarin for thromboembolic stroke prophylaxis in the stroke center, were enrolled. Patient characteristics, blood test results, dietary vitamin K intake, and CYP2C9 and VKORC1 (-1639G>A) genotypes were recorded. CYP2C9 and VKORC1 (-1639G>A) genotyping revealed that 80% of the patients had CYP2C9 *1/*1 and VKORC1 mutant AA genotypes. Multiple linear regression analysis demonstrated that the optimal pharmacogenetics-based model comprised age, body surface area, estimated glomerular filtration rate (eGFR), genotypes, vitamin K intake, aspartate aminotransferase levels, and alcohol intake. eGFR exercised a significant impact on the maintenance doses, as an increase in eGFR of 10 mL/min/1.73 m2 escalated the warfarin maintenance dose by 0.6 mg. Reduced eGFR was related to lower warfarin maintenance doses, independent of VKORC1 and CYP2C9 genotypes in Japanese patients. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

12 pages, 1000 KiB  
Article
Network Protein Interaction in the Link between Stroke and Periodontitis Interplay: A Pilot Bioinformatic Analysis
by Yago Leira, Paulo Mascarenhas, Juan Blanco, Tomás Sobrino, José João Mendes, Vanessa Machado and João Botelho
Genes 2021, 12(5), 787; https://doi.org/10.3390/genes12050787 - 20 May 2021
Cited by 3 | Viewed by 3135
Abstract
The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein–protein network interaction (PPI) search with documented encoded [...] Read more.
The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein–protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and, ultimately, atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

Review

Jump to: Editorial, Research

18 pages, 1025 KiB  
Review
Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries
by Lyudmila V. Dergunova, Ivan B. Filippenkov, Svetlana A. Limborska and Nikolay F. Myasoedov
Genes 2023, 14(5), 953; https://doi.org/10.3390/genes14050953 - 22 Apr 2023
Cited by 10 | Viewed by 3265
Abstract
Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches [...] Read more.
Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein–protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood–brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

35 pages, 567 KiB  
Review
Transcriptomic Studies on Intracranial Aneurysms
by Rafal Morga and Joanna Pera
Genes 2023, 14(3), 613; https://doi.org/10.3390/genes14030613 - 28 Feb 2023
Cited by 2 | Viewed by 1712
Abstract
Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying [...] Read more.
Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying the pathophysiology of IA formation, growth, and rupture remain poorly understood. There are no specific biomarkers of IA presence or rupture. Analysis of expression of mRNA and other RNA types offers a deeper insight into IA pathobiology. Here, we present results of published human studies on IA-focused transcriptomics. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

13 pages, 328 KiB  
Review
Stroke and Etiopathogenesis: What Is Known?
by Tiziana Ciarambino, Pietro Crispino, Erika Mastrolorenzo, Antonello Viceconti and Mauro Giordano
Genes 2022, 13(6), 978; https://doi.org/10.3390/genes13060978 - 30 May 2022
Cited by 9 | Viewed by 3445
Abstract
Background: A substantial portion of stroke risk remains unexplained, and a contribution from genetic factors is supported by recent findings. In most cases, genetic risk factors contribute to stroke risk as part of a multifactorial predisposition. A major challenge in identifying the genetic [...] Read more.
Background: A substantial portion of stroke risk remains unexplained, and a contribution from genetic factors is supported by recent findings. In most cases, genetic risk factors contribute to stroke risk as part of a multifactorial predisposition. A major challenge in identifying the genetic determinants of stroke is fully understanding the complexity of the phenotype. Aims: Our narrative review is needed to improve our understanding of the biological pathways underlying the disease and, through this understanding, to accelerate the identification of new drug targets. Methods: We report, the research in the literature until February 2022 in this narrative review. The keywords are stroke, causes, etiopathogenesis, genetic, epigenetic, ischemic stroke. Results: While better risk prediction also remains a long-term goal, its implementation is still complex given the small effect-size of genetic risk variants. Some authors encourage the use of stroke genetic panels for stroke risk assessment and further stroke research. In addition, new biomarkers for the genetic causes of stroke and new targets for gene therapy are on the horizon. Conclusion: We summarize the latest evidence and perspectives of ischemic stroke genetics that may be of interest to the physician and useful for day-to-day clinical work in terms of both prevention and treatment of ischemic stroke. Full article
(This article belongs to the Special Issue Genomics of Stroke)
15 pages, 1764 KiB  
Review
Influence of Haptoglobin Polymorphism on Stroke in Sickle Cell Disease Patients
by Olivia Edwards, Alicia Burris, Josh Lua, Diana J. Wilkie, Miriam O. Ezenwa and Sylvain Doré
Genes 2022, 13(1), 144; https://doi.org/10.3390/genes13010144 - 14 Jan 2022
Cited by 4 | Viewed by 4537
Abstract
This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The [...] Read more.
This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

11 pages, 3829 KiB  
Review
The Genetic Landscape of Patent Foramen Ovale: A Systematic Review
by Matteo Paolucci, Chiara Vincenzi, Michele Romoli, Giulia Amico, Isabella Ceccherini, Simona Lattanzi, Anna Bersano, Marco Longoni, Simona Sacco, Fabrizio Vernieri, Rosario Pascarella, Franco Valzania and Marialuisa Zedde
Genes 2021, 12(12), 1953; https://doi.org/10.3390/genes12121953 - 6 Dec 2021
Cited by 7 | Viewed by 3791
Abstract
Patent Foramen Ovale (PFO) is a common postnatal defect of cardiac atrial septation. A certain degree of familial aggregation has been reported. Animal studies suggest the involvement of the Notch pathway and other cardiac transcription factors (GATA4, TBX20, NKX2-5) in Foramen Ovale closure. [...] Read more.
Patent Foramen Ovale (PFO) is a common postnatal defect of cardiac atrial septation. A certain degree of familial aggregation has been reported. Animal studies suggest the involvement of the Notch pathway and other cardiac transcription factors (GATA4, TBX20, NKX2-5) in Foramen Ovale closure. This review evaluates the contribution of genetic alterations in PFO development. We systematically reviewed studies that assessed rare and common variants in subjects with PFO. The protocol was registered with PROSPERO and followed MOOSE guidelines. We systematically searched English studies reporting rates of variants in PFO subjects until the 30th of June 2021. Among 1231 studies, we included four studies: two of them assessed the NKX2-5 gene, the remaining reported variants of chromosome 4q25 and the GATA4 S377G variant, respectively. We did not find any variant associated with PFO, except for the rs2200733 variant of chromosome 4q25 in atrial fibrillation patients. Despite the scarceness of evidence so far, animal studies and other studies that did not fulfil the criteria to be included in the review indicate a robust genetic background in PFO. More research is needed on the genetic determinants of PFO. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

12 pages, 271 KiB  
Review
Monogenic Causes of Strokes
by Justyna Chojdak-Łukasiewicz, Edyta Dziadkowiak and Sławomir Budrewicz
Genes 2021, 12(12), 1855; https://doi.org/10.3390/genes12121855 - 23 Nov 2021
Cited by 15 | Viewed by 3460
Abstract
Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene [...] Read more.
Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available. Full article
(This article belongs to the Special Issue Genomics of Stroke)
11 pages, 448 KiB  
Review
Genetic and Genomic Epidemiology of Stroke in People of African Ancestry
by Savvina Prapiadou, Stacie L. Demel and Hyacinth I. Hyacinth
Genes 2021, 12(11), 1825; https://doi.org/10.3390/genes12111825 - 19 Nov 2021
Cited by 10 | Viewed by 2450
Abstract
Stroke is one of the leading causes of disability and death worldwide and places a significant burden on healthcare systems. There are significant racial/ethnic differences in the incidence, subtype, and prognosis of stroke, between people of European and African ancestry, of which only [...] Read more.
Stroke is one of the leading causes of disability and death worldwide and places a significant burden on healthcare systems. There are significant racial/ethnic differences in the incidence, subtype, and prognosis of stroke, between people of European and African ancestry, of which only about 50% can be explained by traditional stroke risk facts. However, only a small number of genetic studies include individuals of African descent, leaving many gaps in our understanding of stroke genetics among this population. This review article highlights the need for and significance of including African-ancestry individuals in stroke genetic studies and points to the efforts that have been made towards this direction. Additionally, we discuss the caveats, opportunities, and next steps in African stroke genetics—a field still in its infancy but with great potential for expanding our understanding of stroke biology and for developing new therapeutic strategies. Full article
(This article belongs to the Special Issue Genomics of Stroke)
Show Figures

Figure 1

Back to TopTop