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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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Abstract—

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.

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Authors and Affiliations

  1. National Medical Research Center for Cardiology, 121552, Moscow, Russia

    G. J. Osmak, N. A. Matveeva, B. V. Titov & O. O. Favorova

  2. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    G. J. Osmak, N. A. Matveeva & O. O. Favorova

Authors
  1. G. J. Osmak
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  2. N. A. Matveeva
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  3. B. V. Titov
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  4. O. O. Favorova
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Correspondence to G. J. Osmak.

Additional information

Translated by M. Novikova

Abbreviations: CI, confident interval; CAD, coronary artery disease; MI, myocardial infarction; OD, odds ratio; CVD, cardiovascular disease; MAF, minor allele frequency; MHC, major histocompatibility complex; SNP, single nucleotide polymorphism; TGFβ, transforming growth factor β.

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Osmak, G.J., Matveeva, N.A., Titov, B.V. et al. The Myocardial Infarction Associated Variant in the MIR196A2 Gene and Presumable Signaling Pathways to Involve miR-196a2 in the Pathological Phenotype. Mol Biol 52, 872–877 (2018). https://doi.org/10.1134/S0026893318060146

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