Hearts (Dec 2023)
Mitochondrial DNA Haplogroups and Variants Predispose to Chagas Disease Cardiomyopathy
- Frédéric Gallardo,
- Pauline Brochet,
- David Goudenège,
- João Paulo Silva Nunes,
- Pauline Andrieux,
- Barbara Maria Ianni,
- Amanda Farage Frade,
- Charles Mady,
- Ronaldo Honorato Barros Santos,
- Andreia Kuramoto,
- Samuel Steffen,
- Antonio Noedir Stolf,
- Pablo Pomerantzeff,
- Alfredo Inacio Fiorelli,
- Edimar Alcides Bocchi,
- Cristina Wide Pissetti,
- Bruno Saba,
- Fabrício C. Dias,
- Marcelo Ferraz Sampaio,
- Fabio Antônio Gaiotto,
- José Antonio Marin-Neto,
- Abílio Fragata,
- Ricardo Costa Fernandes Zaniratto,
- Sergio Siqueira,
- Giselle De Lima Peixoto,
- Fernando Bacal,
- Paula Buck,
- Rafael Ribeiro Almeida,
- Hui Tzu Lin-Wang,
- André Schmidt,
- Mario Hiroyuki Hirata,
- Eduardo Antonio Donadi,
- Alexandre Costa Pereira,
- Virmondes Rodrigues Junior,
- Martino Martinelli,
- Michel Naslavsky,
- Jorge Kalil,
- Vincent Procaccio,
- Edecio Cunha-Neto,
- Christophe Chevillard
Affiliations
- Frédéric Gallardo
- Institut MarMaRa, Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) U1090, Aix Marseille Université, TAGC Theories and Approaches of Genomic Complexity, Parc Scientifique de Luminy, Case 928, 163 Avenue de Luminy, 13288 Marseille, France
- Pauline Brochet
- Institut MarMaRa, Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) U1090, Aix Marseille Université, TAGC Theories and Approaches of Genomic Complexity, Parc Scientifique de Luminy, Case 928, 163 Avenue de Luminy, 13288 Marseille, France
- David Goudenège
- Department of Genetics, University Hospital of Angers, 49933 Angers, France
- João Paulo Silva Nunes
- Institut MarMaRa, Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) U1090, Aix Marseille Université, TAGC Theories and Approaches of Genomic Complexity, Parc Scientifique de Luminy, Case 928, 163 Avenue de Luminy, 13288 Marseille, France
- Pauline Andrieux
- Institut MarMaRa, Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) U1090, Aix Marseille Université, TAGC Theories and Approaches of Genomic Complexity, Parc Scientifique de Luminy, Case 928, 163 Avenue de Luminy, 13288 Marseille, France
- Barbara Maria Ianni
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Amanda Farage Frade
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Charles Mady
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Ronaldo Honorato Barros Santos
- Division of Transplantation, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Andreia Kuramoto
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Samuel Steffen
- Division of Transplantation, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Antonio Noedir Stolf
- Division of Surgery, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Pablo Pomerantzeff
- Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Alfredo Inacio Fiorelli
- Division of Surgery, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Edimar Alcides Bocchi
- Division of Surgery, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Cristina Wide Pissetti
- Laboratory of Immunology, Universidade Federal Do Triângulo Mineiro (UFTM), Uberaba 48036-180, Brazil
- Bruno Saba
- Laboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo 04012-909, Brazil
- Fabrício C. Dias
- School of Medicine of Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto 14049-900, Brazil
- Marcelo Ferraz Sampaio
- Laboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo 04012-909, Brazil
- Fabio Antônio Gaiotto
- Division of Transplantation, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- José Antonio Marin-Neto
- School of Medicine of Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto 14049-900, Brazil
- Abílio Fragata
- Laboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo 04012-909, Brazil
- Ricardo Costa Fernandes Zaniratto
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Sergio Siqueira
- Pacemaker Clinic, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Giselle De Lima Peixoto
- Pacemaker Clinic, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Fernando Bacal
- Division of Transplantation, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Paula Buck
- Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Rafael Ribeiro Almeida
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Hui Tzu Lin-Wang
- Laboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo 04012-909, Brazil
- André Schmidt
- School of Medicine of Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto 14049-900, Brazil
- Mario Hiroyuki Hirata
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil
- Eduardo Antonio Donadi
- School of Medicine of Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto 14049-900, Brazil
- Alexandre Costa Pereira
- Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Virmondes Rodrigues Junior
- Laboratory of Immunology, Universidade Federal Do Triângulo Mineiro (UFTM), Uberaba 48036-180, Brazil
- Martino Martinelli
- Pacemaker Clinic, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-003, Brazil
- Michel Naslavsky
- Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo 05508-090, Brazil
- Jorge Kalil
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Vincent Procaccio
- Department of Genetics, University Hospital of Angers, 49933 Angers, France
- Edecio Cunha-Neto
- Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-903, Brazil
- Christophe Chevillard
- Institut MarMaRa, Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) U1090, Aix Marseille Université, TAGC Theories and Approaches of Genomic Complexity, Parc Scientifique de Luminy, Case 928, 163 Avenue de Luminy, 13288 Marseille, France
- DOI
- https://doi.org/10.3390/hearts4040013
- Journal volume & issue
-
Vol. 4,
no. 4
pp. 97 – 117
Abstract
Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy.
Keywords
