S-EPMC7763522 - <i>BIRC6</i> Is Associated with Vulnerability of Carotid Atherosclerotic Plaque. - OmicsDI

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BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.

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.

SUBMITTER: Alloza I

PROVIDER: S-EPMC7763522 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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<i>BIRC6</i> Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.

Alloza Iraide I Salegi Andrea A Mena Jorge J Navarro Raquel Tulloch RT Martin César C Aspichueta Patricia P Salazar Lucía Martínez LM Carpio Jon Uriarte JU Cagigal Patricia De-la-Hera PD Vega Reyes R Triviño Juan Carlos JC Freijo Maria Del Mar MDM Vandenbroeck Koen K

International journal of molecular sciences 20201209 24

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 (<i>p</i> < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asy ...[more]

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