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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/49724
Acceso en línea:http://hdl.handle.net/10810/49724
Access Level:acceso abierto
Palabra clave:atherosclerosis
carotid plaque
BIRC6
autophagy
red cell distribution width
stroke
Descripción
Sumario: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.

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