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.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Alloza I,Salegi A,Mena J,Navarro RT,Martin C,Aspichueta P,Salazar LM,Carpio JU,Cagigal PD,Vega R,Triviño JC,Freijo MDM,Vandenbroeck Kdoi
10.3390/ijms21249387subject
Has Abstractpub_date
2020-12-09 00:00:00issue
24issn
1422-0067pii
ijms21249387journal_volume
21pub_type
杂志文章abstract：:Activation of the mineralocorticoid receptor (MR) in the heart is considered to be a cardiovascular risk factor. MR activation leads to heart hypertrophy and arrhythmia. In ventricular cardiomyocytes, aldosterone induces a profound remodeling of ion channel expression, in particular, an increase in the expression and ...
journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2012-11-30 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-06-24 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2017-09-19 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2018-09-13 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2018-02-24 00:00:00
