NDLI: BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque

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BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque

Content Provider	MDPI
Author	Juan, Carlos Triviño 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 Freijo, Maria Del Mar Vandenbroeck, Koen
Copyright Year	2020
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.
Starting Page	9387
e-ISSN	14220067
DOI	10.3390/ijms21249387
Journal	International Journal of Molecular Sciences
Issue Number	24
Volume Number	21
Language	English
Publisher	MDPI
Publisher Date	2020-12-09
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Peripheral Vascular Disease Atherosclerosis Carotid Plaque Birc6 Autophagy Red Cell Distribution Width Stroke
Content Type	Text
Resource Type	Article

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