Author:
Brochet Pauline,Ianni Barbara,Laugier Laurie,Frade Amanda Farage,Nunes João Paulo Silva,Teixeira Priscila Camillo,Mady Charles,Ferreira Ludmila Rodrigues Pinto,Ferré Quentin,Santos Ronaldo Honorato Barros,Kuramoto Andreia,Cabantous Sandrine,Steffen Samuel,Stolf Antonio Noedir,Pomerantzeff Pablo,Fiorelli Alfredo Inacio,Bocchi Edimar A,Pissetti Cristina Wide,Saba Bruno,da Silva Cândido Darlan,Dias Fabrício,Sampaio Marcelo,Gaiotto Fabio Antônio,Marin-Neto José Antonio,Fragata Abílio,Zaniratto Ricardo Costa Fernandes,Siqueira Sergio,de lima Peixoto Giselle,Rigaud Vagner Oliveira-Carvalho,Bacal Fernando,Buck Paula,Ribeiro Rafael Almeida,Lin-Wang Hui Tzu,Marin-Neto José Antonio,Schmidt André,Martinelli Martino,Hirata Mario Hiroyuki,Donadi Eduardo,Pereira Alexandre Costa,Rodrigues Virmondes,Puthier Denis,Kalil Jorge,Spinelli Lionel,Cunha-Neto Edecio,Chevillard Christophe
Abstract
AbstractChagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic process remains poorly understood, although genetic and epigenetic factors have already been proposed.Based on bulk RNA-seq and EPIC methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. We identified 4 main biological processes associated with the pathology development, including immune response, ion transport, cardiac muscle processes and nervous system. An in-depth study of the transcription factors binding sites in the differentially methylated regions corroborated the importance of these processes. We also conducted a methylation study on blood to identify potential biomarkers for CCC. Our data revealed 198 differentially methylated positions (DMPs) that could serve as biomarkers of the disease, of which 61 are associated with disease severity.
Publisher
Cold Spring Harbor Laboratory