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BIRC6 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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763522/ https://www.ncbi.nlm.nih.gov/pubmed/33317170 http://dx.doi.org/10.3390/ijms21249387 |
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author | Alloza, Iraide Salegi, Andrea Mena, Jorge Navarro, Raquel Tulloch Martin, César Aspichueta, Patricia Salazar, Lucía Martínez Carpio, Jon Uriarte Cagigal, Patricia De-la-Hera Vega, Reyes Triviño, Juan Carlos Freijo, Maria del Mar Vandenbroeck, Koen |
author_facet | Alloza, Iraide Salegi, Andrea Mena, Jorge Navarro, Raquel Tulloch Martin, César Aspichueta, Patricia Salazar, Lucía Martínez Carpio, Jon Uriarte Cagigal, Patricia De-la-Hera Vega, Reyes Triviño, Juan Carlos Freijo, Maria del Mar Vandenbroeck, Koen |
author_sort | Alloza, Iraide |
collection | PubMed |
description | 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 (p < 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 BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 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 (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 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 (p < 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 BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. |
format | Online Article Text |
id | pubmed-7763522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77635222020-12-27 BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque Alloza, Iraide Salegi, Andrea Mena, Jorge Navarro, Raquel Tulloch Martin, César Aspichueta, Patricia Salazar, Lucía Martínez Carpio, Jon Uriarte Cagigal, Patricia De-la-Hera Vega, Reyes Triviño, Juan Carlos Freijo, Maria del Mar Vandenbroeck, Koen Int J Mol Sci Article 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 (p < 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 BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 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 (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 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 (p < 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 BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability. MDPI 2020-12-09 /pmc/articles/PMC7763522/ /pubmed/33317170 http://dx.doi.org/10.3390/ijms21249387 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alloza, Iraide Salegi, Andrea Mena, Jorge Navarro, Raquel Tulloch Martin, César Aspichueta, Patricia Salazar, Lucía Martínez Carpio, Jon Uriarte Cagigal, Patricia De-la-Hera Vega, Reyes Triviño, Juan Carlos Freijo, Maria del Mar Vandenbroeck, Koen BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title_full | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title_fullStr | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title_full_unstemmed | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title_short | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque |
title_sort | birc6 is associated with vulnerability of carotid atherosclerotic plaque |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763522/ https://www.ncbi.nlm.nih.gov/pubmed/33317170 http://dx.doi.org/10.3390/ijms21249387 |
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