Genetic susceptibility to chronic Chagas disease: An overview of single nucleotide polymorphisms of cytokine genes

Vasconcelos, Romero Henrique Teixeira; Montenegro, Sílvia Maria Lucena; Azevedo, Elisa de Almeida Neves; Gomes, Yara M.; Morais, Clarice Neuenschwander Lins de

doi:10.1016/j.cyto.2012.04.035

Cited by 27 publications

(18 citation statements)

References 53 publications

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“…In humans, infection is characterized by 2 phases: an acute phase, which is generally asymptomatic, and a chronic phase, asymptomatic (indeterminate) or symptomatic T. cruzi genetic variability is increasingly recognized and this parasite has been genetically classified into six discrete typing units (DTUs) -TcI to TcVI (Zingales et al, 2009), -which have different geographic distributions and may be associated with geographically-restricted clinical profiles (Tibayrenc and Telleria, 2010). Several data indicate that human genetic determinants may impact the clinical outcome of Chagas disease (Florez et al, 2012;Vasconcelos et al, 2012). However, a role for genetic variability among the different parasite strains in the diverse clinical outcomes of Chagas disease cannot be excluded.…”

Section: Chagas Disease Is a Neglected Tropical Disease Caused By Thementioning

confidence: 99%

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

et al. 2014

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in:Acta Tropica 139 (2014) pancarditis with inflammatory infiltrates along the epicardium, whereas Sc43 caused inflammation preferentially in the auricles in association with intracellular parasite localization. We observed intramyocardic perivasculitis in mice infected with the VFRA and Y strains, but not with Sc43, during the acute phase, which suggests that endothelial cells may be involved in heart colonization by these more virulent strains. In in vitro infection assays, the Y strain had the highest parasite-cell ratio in epithelial, macrophage and endothelial cell lines, but Y and VFRA strains were higher than Sc43 in cardiomyocytes. Conclusions. This study supports parasite variability as a cause for the diverse cardiac outcomes observed in Chagas disease, and suggests that endothelial cells could be involved in heart infection during the acute phase.3

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Section: Chagas Disease Is a Neglected Tropical Disease Caused By Thementioning

confidence: 99%

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

et al. 2014

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“…Several genes were associated to an increased risk to develop cardiomyopathy (HLA, MHC, TNF, IL1A, IL1B, IL1RN, IL10, IL12B, TIRAP, CCL2, BAT1, LTA, IKBL, CCR5, MIF, IFNG, CXCL9, CXCL10) [25-50]. So far, up to 30 case control studies were done (see for review [51-53]). These studies often led to inconclusive results that may be explained in different ways: a) the use of seronegative subjects as controls which are inadequate controls, since it is unknown whether they were exposed to the pathogen; b) the relatively small size of the study groups which affected the power (the probability) to detect an association; c) the number of tested SNPs; d) the highly heterogeneous genetic background of the study population due to admixture; e) the sex ratio known to exist has not been taken in consideration [54].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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BackgroundChagas 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.MethodsOur 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.ResultsThe 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%.ConclusionsOur 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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“…However, one study performed in familial clusters in Brazil displayed evidence that genetic factors may influence both, seropositivity and cardiac outcome traits, and additional data showed that heritability were 0.56 . In line with this, several genetic variants of immune genes have been analyzed in endemic populations finding some associations to risk to infection and/or differential predisposition to the severity of Chagas disease . To date, only one genome wide association study (GWAS) has been performed on Chagasic patients; nevertheless, due to technical limitations there was not conclusive results indicating any association to severity of disease .…”

Section: Genotype and Allele Distribution Of Foxo3 Rs12212067 Polymormentioning

confidence: 99%

Analysis of association of FOXO3 gene with Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Rodríguez

González

Martín

2016

HLA

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FOXO3, a member of the Forkhead family of proteins, plays a role in controlling immune response. FOXO3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. In this study, we assessed whether this FOXO3 gene polymorphism is related to susceptibility to infection by Trypanosoma cruzi and/or chronic Chagasic cardiomyopathy. A total of 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and chronic Chagasic cardiomyopathy (n = 401) were genotyped for the FOXO3 rs12212067 using TaqMan allelic discrimination. Our results showed no statistically significantly differences between allelic and genotypic frequencies of rs12212067 in seronegative individuals compared with seropositive individuals. Similarly, we observed no evidence of association when asymptomatic individuals were compared with chronic Chagasic cardiomyopathy patients. Our data suggest that the FOXO3 genetic variant rs12212067 do not play an important role in Chagas disease.

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Genetic susceptibility to chronic Chagas disease: An overview of single nucleotide polymorphisms of cytokine genes

Cited by 27 publications

References 53 publications

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

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

Analysis of association of FOXO3 gene with Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

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