Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783628038289752064
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
work_keys_str_mv AT allozairaide birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT salegiandrea birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT menajorge birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT navarroraqueltulloch birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT martincesar birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT aspichuetapatricia birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT salazarluciamartinez birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT carpiojonuriarte birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT cagigalpatriciadelahera birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT vegareyes birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT trivinojuancarlos birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT freijomariadelmar birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque
AT vandenbroeckkoen birc6isassociatedwithvulnerabilityofcarotidatheroscleroticplaque