GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

Casares-Marfil, Desiré; Kerick, Martin; Andrés-León, Eduardo; Bosch-Nicolau, Pau; Romero, Israel Molina; Martı́n, Javier; Acosta‐Herrera, Marialbert

doi:10.1371/journal.pntd.0009874

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…More precisely, all the previously described biological process seems to be linked to the immune response, and notably to the Th1 response, including IFN-γ and RUNX3. These results, combined with those obtained in previous analyses of CCC ( 9 , 78 ), confirm the importance of DNA methylation in the development of CCC.…”

Section: Discussionsupporting

confidence: 88%

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

et al. 2022

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Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS’s DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

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Section: Discussionsupporting

confidence: 88%

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

et al. 2022

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“…It is particularly applied to understanding the genetic basis of complex traits and diseases. Furthermore, it has also been successfully used to study mQTLs (methylation QTLs) and thus relate changes in the methylation of CpG sites, usually in gene regulatory regions, to polymorphic variations [38] .…”

Section: Omics Integration Toolsmentioning

confidence: 99%

A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data

Borrego-Yaniz,

Terrón-Camero,

Kerick

et al. 2024

Computational and Structural Biotechnology Journal

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“…We also note the few members of the set of phospholipase A and acyltransferase paralogs (PLAAT1, 2 and 4) that lack a CVD-related bibliography (see Table 2), while PLAAT3 (a.k.a. PLA2G16) has been found in a GWAS study associated with Chagas cardiomyopathy [37] and was the most downregulated gene in calf muscle of patients diagnosed with peripheral artery disease (PAD) [38].…”

Section: Uniprot Score Protein Name Gene Id Cvd Referencesmentioning

confidence: 99%

A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities

Anyaegbunam,

More,

Fontaine

et al. 2023

CIMB

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Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid–protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

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GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

Cited by 6 publications

References 45 publications

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data

A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities

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