Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

摘要: Background: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic cardiomyopathy (CCC), an inflammatory dilated that is, far, most important clinical consequence T. infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested familial aggregation cases and association markers innate adaptive immunity genes with CCC development. Migration Th1-type T cells play a major role myocardial damage. Methods: Our analysis focused on CCR5, CCL2 MAL/TIRAP genes. We used Tag SNPs based approach, defined catch all information from each gene. study conducted large Brazilian population including 315 118 ASY subjects. Results: CCL2rs2530797A/A TIRAPrs8177376A/A were associated increase susceptibility whereas CCR5rs3176763C/C genotype protection CCC. These associations confirmed when we restricted severe CCC, characterized left ventricular ejection fraction under 40%. Conclusions: data show polymorphisms affecting key molecules involved several immune parameters (innate signal transduction cell/monocyte migration) This also points out multigenic character polymorphism imparting small contribution. identification for will provide pathogenesis as well therapeutic targets.