Genomic medicine in Chagas disease

Acosta‐Herrera, Marialbert; Strauss, Mariana; Casares-Marfil, Desiré; Martı́n, Javier

doi:10.1016/j.actatropica.2019.105062

Cited by 19 publications

(16 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Host genetic factors have been suggested to play an important role in the susceptibility to Chagas disease. [6–9]. Polymorphism in genes encoding cytokines may influence the level of cytokines production and, consequently, cause different immunological responses [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations

et al. 2019

Self Cite

View full text Add to dashboard Cite

Host genetic factors have been suggested to play an important role in the susceptibility to Chagas disease. Given the influence of interleukin 18 (IL-18) in the development of the disease, in the present study, we analyzed three IL18 genetic variants (rs2043055, rs1946518, rs360719) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC), in different Latin America populations. Genetic data of 3,608 patients from Colombia, Bolivia, Argentina, and Brazil were meta-analyzed to validate previous findings with increased statistical power. Seropositive and seronegative individuals were compared for T. cruzi infection susceptibility. In the Colombian cohort, the allelic frequencies of the three variants showed a significant association, with adjustment for sex and age, and also after applying multiple testing adjustments. Among the Colombian and Argentinean cohorts, rs360719 showed a significant genetic effect in a fixed-effects meta-analysis after a Bonferroni correction (OR: 0.76, CI: 0.66–0.89, P = 0.001). For CCC, the rs2043055 showed an association with protection from cardiomyopathy in the Colombian cohort (OR: 0.79, CI: 0.64–0.99, P = 0.037), with adjustment for sex and age, and after applying multiple testing adjustments. The meta-analysis of the CCC vs. asymptomatic patients from the four cohorts showed no evidence of association. In conclusion, our results validated the association found previously in the Colombian cohort suggesting that IL18 rs360719 plays an important role in the susceptibility to T. cruzi infection and no evidence of association was found between the IL18 genetic variants and CCC in the Latin American population studied.

show abstract

Section: Introductionmentioning

confidence: 99%

Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…150 case-control genetic association studies addressing polymorphisms in 76 genes, which disclosed 62 SNPs from 44 genes to be associated with CCC, mostly related to immunology and inflammation. From those, a much smaller number of SNPs were associated with CCC severity (ventricular dysfunction) ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy

et al. 2020

View full text Add to dashboard Cite

Frade-Barros et al. Polymorphisms and Chagas Disease Cardiomyopathy 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development. Conclusions: Our data show that novel polymorphisms affecting IL12B and IL10, but not IFNG or IL4 genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-γ production associated with CCC is genetically controlled.

show abstract

“…Goes et al found a possible explanation for this discrepancy; parasites need minimal levels of ROS, which would work as a signal for replication, but high levels of ROS are deleterious to the parasite, inducing, for example, DNA damage [ 31 ]. This highlights the importance of the background of the host in the outcome of the infection [ 2 , 34 ]. Interestingly, by proteomic analysis, we have reported enriched antioxidant defenses in trypomastigotes of VFRA compared to Y strain [ 35 ], that could support the hypothesis that ROS production is detrimental for VFRA and for this reason VFRA would tend to increase these metabolic pathways to cope with the great generation of ROS by NOX2 among other enzymes.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

et al. 2020

View full text Add to dashboard Cite

The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/compared to BALB/c in 5 out of 6 strains. However, Slamf1-/macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease.

show abstract

Genomic medicine in Chagas disease

Cited by 19 publications

References 145 publications

Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations

Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations

Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy

Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

Contact Info

Product

Resources

About