Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy

Autor: Frade, Amanda Farage, Teixeira, Priscila Camilo, Ianni, Barbara Maria, Pissetti, Cristina Wide, Saba, Bruno, Tzu Wang, Lin Hui, Kuramoto, Andreia, Nogueira, Luciana Gabriel, Buck, Paula, Dias, Fabrício, Giniaux, Helene, Llored, Agnes, Alves, Sthefanny, Schmidt, Andre, Donadi, Eduardo, Marin-Neto, Jose Antonio, Hirata, Mario, Sampaio, Marcelo, Fragata, Abílio, Bocchi, Edimar Alcides, Stolf, Antonio Noedir, Fiorelli, Alfredo Inacio, Barros Santos, Ronaldo Honorato, Rodrigues, Virmondes, Pereira, Alexandre Costa, Kalil, Jorge, Cunha-Neto, Edecio, Chevillard, Christophe
Přispěvatelé: Heart Institute (SAO PAULO - Heart Institute), University of São Paulo Medical School, Universidade Federal do Triângulo Mineiro Uberaba, Instituto de Cardiologia Dante Pazzanese (IDPC), Heart Institute (InCor), Universidade de São Paulo (USP)-Faculdade de Medicina FMUSP, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo (USP), Aix Marseille Université (AMU), Department of Allergy and Clinical Immunology [São Paulo, Brazil], Hospital Sírio-Libanês [São Paulo, Brazil], Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), Institute for Investigation in Immunology (III), National Institute of Science and Technology (INCT), Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, Génétique et immunologie des maladies parasitaires (GIMP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Universidade de São Paulo = University of São Paulo (USP)-Faculdade de Medicina FMUSP, Universidade de São Paulo = University of São Paulo (USP), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2013, 8 (12), ⟨10.1371/journal.pone.0083446⟩
PLoS ONE, Vol 8, Iss 12, p e83446 (2013)
PLoS ONE, 2013, 8 (12), ⟨10.1371/journal.pone.0083446⟩
ISSN: 1932-6203
Popis: International audience; AimsChagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis.Methods and ResultsWe conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful.ConclusionsGenetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.
Databáze: OpenAIRE
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