Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.
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История · было → стало
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Niskanen Julia E, Ohlsson Åsa, Ljungvall Ingrid, Drögemüller Michaela, Ernst Robert F, Dooijes Dennis, van Deutekom Hanneke W M, van Tintelen J Peter, Snijders Blok Christian J B, van Vugt Marion, van Setten Jessica, Asselbergs Folkert W, Petrič Aleksandra Domanjko, Salonen Milla, Hundi Sruthi, Hörtenhuber Matthias, DoGA consortium, Kere Juha, Pyle W Glen, Donner Jonas, Postma Alex V, Leeb Tosso, Andersson Göran, Hytönen Marjo K, Häggström Jens, Wiberg Maria, Friederich Jana, Eberhard Jenny, Harakalova Magdalena, van Steenbeek Frank G, Wess Gerhard, Lohi Hannes
Аннотация
METHODS: We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.
RESULTS: Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.
CONCLUSIONS: Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.