Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways. - Archive ouverte HAL Access content directly
Journal Articles BMC Infectious Diseases Year : 2013

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

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Cristina Wide Pissetti
  • Function : Author
  • PersonId : 950025
Barbara Maria Ianni
  • Function : Author
  • PersonId : 950026
Bruno Saba
  • Function : Author
  • PersonId : 950027
Hui Tzu Lin-Wang
  • Function : Author
  • PersonId : 950028
Ariana de Melo Borges
  • Function : Author
  • PersonId : 950030
Paula Buck
  • Function : Author
  • PersonId : 950031
Fabrício Dias
  • Function : Author
  • PersonId : 950032
Monique Baron
  • Function : Author
  • PersonId : 950033
Ludmila Rodrigues Pinto Ferreira
  • Function : Author
  • PersonId : 950034
Andre Schmidt
  • Function : Author
  • PersonId : 950035
Mario Hirata
  • Function : Author
  • PersonId : 950037
Marcelo Sampaio
  • Function : Author
  • PersonId : 950038
Abílio Fragata
  • Function : Author
  • PersonId : 950039
Alexandre Costa Pereira
  • Function : Author
  • PersonId : 950040
Eduardo Donadi
  • Function : Author
  • PersonId : 950041
Virmondes Rodrigues
  • Function : Author
  • PersonId : 950043

Abstract

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

inserm-00920392 , version 1 (18-12-2013)

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Amanda Farage Frade, Cristina Wide Pissetti, Barbara Maria Ianni, Bruno Saba, Hui Tzu Lin-Wang, et al.. Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways.. BMC Infectious Diseases, 2013, 13 (1), pp.587. ⟨10.1186/1471-2334-13-587⟩. ⟨inserm-00920392⟩
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