Chagas disease, caused by Trypanosoma cruzi, affects 15 million people; from these, 30% develop myocarditis and Chronic Chagas disease cardiomyopathy (CCC) while most patients remain asymptomatic (ASY). Familial aggregation of CCC cases and the association of single nucleotide polymorphisms (SNP) with CCC suggests a genetic component to disease susceptibility. The outcome of Chagas disease is ultimately defined in the patients' hearts, a consequence of inflammation and myocardial response. We hypothesize that expression of many pathogenetically relevant genes/ proteins in the myocardium of CCC patients is controlled by genetic polymorphisms, and that a genetic signature based on such polymorphic genes can have a prognostic value. In Aim 1, we will use a systems biology approach to identify genes/proteins differentially expressed in CCC myocardium, using proteomic and transcriptomic analysis. In aim 2, we will identify genetic variants associated to disease. A case-control study will use large main and replication cohorts (CCC cases and ASY controls). Common Tag single SNP from genes identified in Aim 1 will be genotyped and analyzed. Exome sequencing will be used in multicase nuclear families, to identify rare variants shared only by CCC cases. Functional analyses on SNPs will be performed. Combinations of multiple SNPs may have a prognostic value at the individual patient levei, allowing close follow-up. Moreover, this study will provide significant information on pathogenesis and disease progression. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
PINTO FERREIRA, LUDMILA RODRIGUES;
FERREIRA, FREDERICO MORAES;
NAKAYA, HELDER IMOTO;
CNDIDO, DARLAN DA SILVA;
DE OLIVEIRA, LEA CAMPOS;
LANTERI, MARION C.;
RIGAUD, VAGNER OLIVEIRA-CARVALHO;
RIBEIRO, ANTONIO LUIZ P.;
SABINO, ESTER CERDEIRA;
Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.
Journal of Infectious Diseases,
FEB 1 2017.
Web of Science Citations: 11.