rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.
SNP
atherosclerosis
coronary artery disease
genetics
microRNA
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
revised:
24
08
2021
received:
03
02
2021
accepted:
24
08
2021
pubmed:
23
9
2021
medline:
26
10
2021
entrez:
22
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34551209
doi: 10.15252/emmm.202114060
pmc: PMC8495461
doi:
Substances chimiques
MIRN143 microRNA, human
0
MIRN145 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14060Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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