BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
View/ Open
Date
2020-12-09Author
Alloza Moral, Iraide
Salegi, Andrea
Mena Lucía, Jorge
Tulloch Navarro, Raquel
Martín Plágaro, César Augusto
Aspichueta Celaá, Patricia
Martínez Salazar, Lucía
Uriarte Carpio, Jon
De la Hera Cagigal, Patricia
Vega Manrique, Reyes
Triviño, Juan Carlos
Freijo, María del Mar
Vandenbroeck, Koen
Metadata
Show full item record
International Journal of Molecular Sciences 21(24) : (2020) // Article ID9387
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 (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.
Collections
Except where otherwise noted, this item's license is described as 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/).