Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/5090
Title: Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy
Authors: FRADE, Amanda FarageTEIXEIRA, Priscila CamiloIANNI, Barbara MariaPISSETTI, Cristina WideSABA, BrunoWANG, Lin Hui TzuKURAMOTO, AndreiaNOGUEIRA, Luciana GabrielBUCK, PaulaDIAS, FabricioGINIAUX, HeleneLLORED, AgnesALVES, SthefannySCHMIDT, AndreDONADI, EduardoMARIN-NETO, Jose AntonioHIRATA, MarioSAMPAIO, MarceloFRAGATA, AbilioBOCCHI, Edimar AlcidesSTOLF, Antonio NoedirFIORELLI, Alfredo InacioSANTOS, Ronaldo Honorato BarrosRODRIGUES, VirmondesPEREIRA, Alexandre CostaKALIL, JorgeCUNHA-NETO, EdecioCHEVILLARD, Christophe
Citation: PLOS ONE, v.8, n.12, 2013
Abstract: Aims: Chagas 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 Results: We 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. Conclusions: Genetic 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.
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Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MCP
Departamento de Cardio-Pneumologia - FM/MCP

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/11
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação

Artigos e Materiais de Revistas Científicas - LIM/13
LIM/13 - Laboratório de Genética e Cardiologia Molecular

Artigos e Materiais de Revistas Científicas - LIM/19
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular


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