Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways.
BMC Infect Dis
; 13: 587, 2013 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-24330528
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Trypanosoma cruzi
/
Glicoproteínas de Membrana
/
Cardiomiopatia Chagásica
/
Receptores de Interleucina-1
/
Quimiocina CCL2
/
Receptores CCR5
/
Predisposição Genética para Doença
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País como assunto:
America do sul
/
Brasil
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article