The Myocardial Infarction Associated Variant in the MIR196A2 Gene and Presumable Signaling Pathways to Involve miR-196a2 in the Pathological Phenotype


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Resumo

The heritable component of susceptibility to myocardial infraction (MI) remains unexplained, possibly due to the minor effects of genes, which are not obviously associated with the disease. These genes may be integrated in miRNA regulated networks associated with myocardial infarction. A systematic review of the literature led us to selecting rs2910164 (MIR146A), rs11614913 (MIR196A2), and rs3746444 (MIR499А) variants to study the association with the MI phenotype. In ethnic Russians, variant rs11614913*C (MIR196A2) was found to be associated with the risk of myocardial infraction (p = 0.023, OR = 1.74) for the first time; this association was validated in an independent cohort. The gene-gene interaction network for experimentally validated miR-196a2 target genes was built and analyzed. One of its four topological clusters contained the majority of miR-196a2 target genes associated with atherosclerosis, coronary artery disease or myocardial infarction and was enriched with the genes regulating the TGFβ and class I MHC signaling pathways, platelet activation/aggregation, and the cell cycle control. This analysis points towards the role of miR-196a2 in the pathological coronary phenotypes and opens up an avenue for further investigations.

Sobre autores

G. Osmak

National Medical Research Center for Cardiology; Pirogov Russian National Research Medical University

Autor responsável pela correspondência
Email: german.osmak@gmail.com
Rússia, Moscow, 121552; Moscow, 117997

N. Matveeva

National Medical Research Center for Cardiology; Pirogov Russian National Research Medical University

Email: german.osmak@gmail.com
Rússia, Moscow, 121552; Moscow, 117997

B. Titov

National Medical Research Center for Cardiology

Email: german.osmak@gmail.com
Rússia, Moscow, 121552

O. Favorova

National Medical Research Center for Cardiology; Pirogov Russian National Research Medical University

Email: german.osmak@gmail.com
Rússia, Moscow, 121552; Moscow, 117997

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