<i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants...
Ausführliche Beschreibung
Autor*in: |
Iraide Alloza [verfasserIn] Andrea Salegi [verfasserIn] Jorge Mena [verfasserIn] Raquel Tulloch Navarro [verfasserIn] César Martin [verfasserIn] Patricia Aspichueta [verfasserIn] Lucía Martínez Salazar [verfasserIn] Jon Uriarte Carpio [verfasserIn] Patricia De-la-Hera Cagigal [verfasserIn] Reyes Vega [verfasserIn] Juan Carlos Triviño [verfasserIn] Maria del Mar Freijo [verfasserIn] Koen Vandenbroeck [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
In: International Journal of Molecular Sciences - MDPI AG, 2003, 21(2020), 24, p 9387 |
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Übergeordnetes Werk: |
volume:21 ; year:2020 ; number:24, p 9387 |
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Link aufrufen |
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DOI / URN: |
10.3390/ijms21249387 |
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Katalog-ID: |
DOAJ057059330 |
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520 | |a Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. | ||
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10.3390/ijms21249387 doi (DE-627)DOAJ057059330 (DE-599)DOAJ571715dc313643a6aef7a55929067293 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Iraide Alloza verfasserin aut <i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. atherosclerosis carotid plaque <i<BIRC6</i< autophagy red cell distribution width stroke Biology (General) Chemistry Andrea Salegi verfasserin aut Jorge Mena verfasserin aut Raquel Tulloch Navarro verfasserin aut César Martin verfasserin aut Patricia Aspichueta verfasserin aut Lucía Martínez Salazar verfasserin aut Jon Uriarte Carpio verfasserin aut Patricia De-la-Hera Cagigal verfasserin aut Reyes Vega verfasserin aut Juan Carlos Triviño verfasserin aut Maria del Mar Freijo verfasserin aut Koen Vandenbroeck verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 24, p 9387 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:24, p 9387 https://doi.org/10.3390/ijms21249387 kostenfrei https://doaj.org/article/571715dc313643a6aef7a55929067293 kostenfrei https://www.mdpi.com/1422-0067/21/24/9387 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 24, p 9387 |
spelling |
10.3390/ijms21249387 doi (DE-627)DOAJ057059330 (DE-599)DOAJ571715dc313643a6aef7a55929067293 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Iraide Alloza verfasserin aut <i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. atherosclerosis carotid plaque <i<BIRC6</i< autophagy red cell distribution width stroke Biology (General) Chemistry Andrea Salegi verfasserin aut Jorge Mena verfasserin aut Raquel Tulloch Navarro verfasserin aut César Martin verfasserin aut Patricia Aspichueta verfasserin aut Lucía Martínez Salazar verfasserin aut Jon Uriarte Carpio verfasserin aut Patricia De-la-Hera Cagigal verfasserin aut Reyes Vega verfasserin aut Juan Carlos Triviño verfasserin aut Maria del Mar Freijo verfasserin aut Koen Vandenbroeck verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 24, p 9387 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:24, p 9387 https://doi.org/10.3390/ijms21249387 kostenfrei https://doaj.org/article/571715dc313643a6aef7a55929067293 kostenfrei https://www.mdpi.com/1422-0067/21/24/9387 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 24, p 9387 |
allfields_unstemmed |
10.3390/ijms21249387 doi (DE-627)DOAJ057059330 (DE-599)DOAJ571715dc313643a6aef7a55929067293 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Iraide Alloza verfasserin aut <i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. atherosclerosis carotid plaque <i<BIRC6</i< autophagy red cell distribution width stroke Biology (General) Chemistry Andrea Salegi verfasserin aut Jorge Mena verfasserin aut Raquel Tulloch Navarro verfasserin aut César Martin verfasserin aut Patricia Aspichueta verfasserin aut Lucía Martínez Salazar verfasserin aut Jon Uriarte Carpio verfasserin aut Patricia De-la-Hera Cagigal verfasserin aut Reyes Vega verfasserin aut Juan Carlos Triviño verfasserin aut Maria del Mar Freijo verfasserin aut Koen Vandenbroeck verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 24, p 9387 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:24, p 9387 https://doi.org/10.3390/ijms21249387 kostenfrei https://doaj.org/article/571715dc313643a6aef7a55929067293 kostenfrei https://www.mdpi.com/1422-0067/21/24/9387 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 24, p 9387 |
allfieldsGer |
10.3390/ijms21249387 doi (DE-627)DOAJ057059330 (DE-599)DOAJ571715dc313643a6aef7a55929067293 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Iraide Alloza verfasserin aut <i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. atherosclerosis carotid plaque <i<BIRC6</i< autophagy red cell distribution width stroke Biology (General) Chemistry Andrea Salegi verfasserin aut Jorge Mena verfasserin aut Raquel Tulloch Navarro verfasserin aut César Martin verfasserin aut Patricia Aspichueta verfasserin aut Lucía Martínez Salazar verfasserin aut Jon Uriarte Carpio verfasserin aut Patricia De-la-Hera Cagigal verfasserin aut Reyes Vega verfasserin aut Juan Carlos Triviño verfasserin aut Maria del Mar Freijo verfasserin aut Koen Vandenbroeck verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 24, p 9387 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:24, p 9387 https://doi.org/10.3390/ijms21249387 kostenfrei https://doaj.org/article/571715dc313643a6aef7a55929067293 kostenfrei https://www.mdpi.com/1422-0067/21/24/9387 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 24, p 9387 |
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<i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
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Iraide Alloza |
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International Journal of Molecular Sciences |
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International Journal of Molecular Sciences |
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eng |
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Iraide Alloza Andrea Salegi Jorge Mena Raquel Tulloch Navarro César Martin Patricia Aspichueta Lucía Martínez Salazar Jon Uriarte Carpio Patricia De-la-Hera Cagigal Reyes Vega Juan Carlos Triviño Maria del Mar Freijo Koen Vandenbroeck |
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Elektronische Aufsätze |
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Iraide Alloza |
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10.3390/ijms21249387 |
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verfasserin |
title_sort |
<i<birc6</i< is associated with vulnerability of carotid atherosclerotic plaque |
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QH301-705.5 |
title_auth |
<i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
abstract |
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. |
abstractGer |
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. |
abstract_unstemmed |
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (<i<p</i< < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the <i<BIRC6</i< (<i<BRUCE</i</<i<Apollon</i<) gene, rs35286811, emerged as significantly associated with CVA symptomatology (<i<p</i< = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (<i<p</i< < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (<i<p</i< < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (<i<p</i< < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces <i<BIRC6</i< as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. |
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container_issue |
24, p 9387 |
title_short |
<i<BIRC6</i< Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
url |
https://doi.org/10.3390/ijms21249387 https://doaj.org/article/571715dc313643a6aef7a55929067293 https://www.mdpi.com/1422-0067/21/24/9387 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067 |
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Andrea Salegi Jorge Mena Raquel Tulloch Navarro César Martin Patricia Aspichueta Lucía Martínez Salazar Jon Uriarte Carpio Patricia De-la-Hera Cagigal Reyes Vega Juan Carlos Triviño Maria del Mar Freijo Koen Vandenbroeck |
author2Str |
Andrea Salegi Jorge Mena Raquel Tulloch Navarro César Martin Patricia Aspichueta Lucía Martínez Salazar Jon Uriarte Carpio Patricia De-la-Hera Cagigal Reyes Vega Juan Carlos Triviño Maria del Mar Freijo Koen Vandenbroeck |
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up_date |
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