Polymorphism in the alpha cardiac muscle actin 1 geneIs associated to susceptibility to chronic inflammatory cardiomyopathy
PLos ONE
; 8(12): 1-16, 2013. ilus
Artigo
em Inglês
| Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1065112
Biblioteca responsável:
BR79.1
Localização: BR79.1
ABSTRACT
Aims:
Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to alife-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infectedindividuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to diseaseprogression was suggested by familial aggregation of cases and the association of markers of innate and adaptiveimmunity 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 ACTC1gene in CCC pathogenesis.Methods andResults:
We conducted a proteomic and genetic study on a Brazilian study population. The geneticstudy was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and thereplication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower inmyocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping acase-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1gene identified rs640249 SNP, located at the 5 region, as associated to CCC. Associations are borderline aftercorrection 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 thepromoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replicationcohort will be useful.Conclusions:
Genetic variations at the ACTC1 gene may contribute to progression to chronic ChagasCardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1promoter regions.
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Coleções:
Bases de dados nacionais
/
Brasil
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
/
Doenças Negligenciadas
Problema de saúde:
Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
/
Doença de Chagas
/
Doenças Negligenciadas
Base de dados:
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Assunto principal:
Variação Genética
/
Cardiomiopatia Chagásica
/
Doença de Chagas
Tipo de estudo:
Estudo prognóstico
/
Fatores de risco
Idioma:
Inglês
Revista:
PLos ONE
Ano de publicação:
2013
Tipo de documento:
Artigo
Instituição/País de afiliação:
Aix-Marseille Université/FR
/
Escola de Medicina de Ribeirão Preto/BR
/
Instituto Dante Pazzanese de Cardiologia/BR
/
Instituto do Coração/BR
/
Universidade Federal do Triângulo Mineiro/BR
/
Universidade de São Paulo/BR