Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

Amanda Priscila De Oliveira,Eumildo De Campos Júnior,Carlos Eugênio Cavasini,Reinaldo Bulgarelli Bestetti,Cinara Cássia Brandão De Mattos,Luiz Carlos De Mattos,João Gomes Netinho,Aldenis Albaneze Borim,Luiz Sérgio Ronchi,Lílian Castiglioni,Ana Vitória Da Silveira Camargo,Cássia Rubia Bernardo,Edecio Cunha-Neto

doi:10.1371/journal.pone.0141847

Amanda Priscila De Oliveira, Eumildo De Campos Júnior + Show 11 more

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https://doi.org/10.1371/journal.pone.0141847

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Abstract

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region—rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Highlights

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and, due to migration, it has spread to other countries [1,2,3]
The clinical manifestations of the disease occur approximately two decades after infection with about 30% of infected individuals developing the cardiac form of the disease, chronic Chagas heart disease (CCHD)
We evaluated the possible association between the genotypes and alleles with the severity of left ventricular systolic dysfunction (LVSD) in patients with CCHD

Summary

Introduction

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and, due to migration, it has spread to other countries [1,2,3]. The clinical manifestations of the disease occur approximately two decades after infection with about 30% of infected individuals developing the cardiac form of the disease, chronic Chagas heart disease (CCHD). In this case, chronic heart failure is the most important clinical manifestation of the disease [8]. Genetic variants of cytokines are involved in the different clinical manifestations of the disease. Chemokines are cytokines formed by small proteins involved in the recruitment of leukocytes to inflammation sites. Several types of chemokine receptors are expressed in leukocytes. The CC chemokine receptor 5 (CCR5), ligand of the CCL3, CCL4, and CCL5 chemokines, is expressed by monocytes, macrophages and T lymphocytes, preferentially on TH1 cells [13,14,15,16]

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