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- Title
BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.
- Authors
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
- 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.
- Subjects
ATHEROSCLEROTIC plaque; VASCULAR smooth muscle; ERYTHROCYTES; STROKE; MUSCLE cells; SINGLE nucleotide polymorphisms
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 24, p9387
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21249387