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SHR Neuro Cancer Cardio Lipid Metab Microb

Hall, IF; Climent, M; Anselmi, CV; Papa, L; Tragante, V; Lambroia, L; Farina, FM; Kleber, ME; Marz, W; Biguori, C; Condorelli, G; Elia, L.
rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk
EMBO MOL MED. 2021; e14060 Doi: 10.15252/emmm.202114060 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

März Winfried

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Abstract:

The role of single nucleotide polymorphisms (SNPs) in the etiopathogenesis of cardiovascular diseases is well known. The effect of SNPs on disease predisposition has been established not only for protein coding genes but also for genes encoding microRNAs (miRNAs). The miR-143/145 cluster is smooth muscle cell-specific and implicated in the pathogenesis of atherosclerosis. Whether SNPs within the genomic sequence of the miR-143/145 cluster are involved in cardiovascular disease development is not known. We thus searched annotated sequence databases for possible SNPs associated with miR-143/145. We identified one SNP, rs41291957 (G > A), located -91 bp from the mature miR-143 sequence, as the nearest genetic variation to this miRNA cluster, with a minor allele frequency > 10%. In silico and in vitro approaches determined that rs41291957 (A) upregulates miR-143 and miR-145, modulating phenotypic switching of vascular smooth cells towards a differentiated/contractile phenotype. Finally, we analysed association between rs41291957 and CAD in two cohorts of patients, finding that the SNP was a protective factor. In conclusion, our study links a genetic variation to a pathological outcome through involvement of miRNAs.

Find related publications in this database (Keywords)

atherosclerosis

coronary artery disease

genetics

microRNA

SNP

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