International journal of molecular sciences, 2020-12, Vol.21 (24), p.9387
2020
Details
- Autor(en) / Beteiligte
- Titel
- BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
- Ist Teil von
- International journal of molecular sciences, 2020-12, Vol.21 (24), p.9387
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 ( < 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 ( / ) gene, rs35286811, emerged as significantly associated with CVA symptomatology ( = 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 ( < 0.0001), and significantly higher in carriers of the rs35286811 risk allele ( < 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 ( < 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 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms21249387Titel-ID: cdi_doaj_primary_oai_doaj_org_article_571715dc313643a6aef7a55929067293
- Format
- –
- Schlagworte
- Amino acids, Apollon, Apoptosis, Arteriosclerosis, Asymptomatic, Atherosclerosis, Autophagy, BIRC6, Cardiovascular disease, Carotid Arteries - metabolism, Carotid Arteries - pathology, carotid plaque, Gene expression, Genomes, Genotype & phenotype, Humans, Inhibitor of Apoptosis Proteins - genetics, mRNA, Muscles, Nucleotides, Phagocytosis, Plaque, Atherosclerotic - genetics, Plaque, Atherosclerotic - metabolism, Plaque, Atherosclerotic - pathology, Polymorphism, Single Nucleotide, red cell distribution width, Risk analysis, Risk factors, Single-nucleotide polymorphism, Smooth muscle, Stroke, Trends