Mitochondrial DNA haplogroups and variants predispose to chagas disease cardiomyopathy
Hearts
; 4(4): 97-117, dez.2023. ilus
Artículo
en Inglés
| CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1530621
Biblioteca responsable:
BR79.1
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.
Texto completo:
Disponible
Colección:
Bases de datos nacionales
/
Brasil
Contexto en salud:
ODS3 - Salud y Bienestar
/
Enfermedades Desatendidas
Problema de salud:
Meta 3.3: Poner fin a las enfermedades desatendidas y detener enfermedades transmisibles
/
Enfermedad de Chagas
/
Enfermedades Desatendidas
Base de datos:
CONASS
/
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Idioma:
Inglés
Revista:
Hearts
Año:
2023
Tipo del documento:
Artículo
Institución/País de afiliación:
Faculdade de Medicina de Ribeirão Preto (FMRP)/BR
/
Heart Institute Instituto do Coração (InCor)/BR
/
Institut National de la Santé Et de la Recherche Médicale (INSERM)/FR
/
Instituto de Cardiologia Dante Pazzanese (IDPC)/BR
/
Laboratory of Immunology, Heart Institute Instituto do Coração (InCor/BR
/
Universidade Federal Do Triângulo Mineiro (UFTM)/BR
/
University Hospital of Angers/FR
/
University of São Paulo (USP)/BR
/
University of São Paulo/BR