Avaliação de polimorfismos genéticos como biomarcadores na evolução da cardiomiopatia chagásica / Evaluation of genetic polymorphisms as biomarkers in the evolution of Chagas cardiomyopathy

RESUMO

O Trypanosoma cruzi é um parasita intracelular e agente causador da doença de Chagas, que afeta milhões de pessoas em todo o mundo. Sabe-se que durante os processos de inflamação, regeneração e fibrose desencadeados pelo T. cruzi no hospedeiro há a participação de diversos mediadores e fatores. O objetivo deste trabalho foi avaliar a associação entre polimorfismos de nucleotídeos únicos com as formas clínicas e o grau de fibrose em pacientes com doença de Chagas. Os polimorfismos foram analisados por PCR em tempo real. Foram incluídos no estudo 55 pacientes com diagnóstico de doença de Chagas e classificados de acordo com a forma clínica da doença, sendo que 17 apresentavam a forma indeterminada, 15 a forma cardíaca sem disfunção ventricular e 23 a forma cardíaca com disfunção ventricular. Os genótipos CA dos polimorfismos do gene LGALS3 (rs4644 e rs4652); AG e GG do SOCS3 (rs4969170); CT e TT do IL-28B (rs12979860 e 8099917, respectivamente); AG, AG, CC, AG e AG do CLDN-1 (rs10212165, rs3909582, rs9865082, rs9880018 e rs9848283, respectivamente); e CC do CCL5 (rs2280789) foram estatisticamente mais frequentes em pacientes com a forma cardíaca do que com a forma indeterminada da doença. Com relação ao grau de fibrose, os genótipos CC dos polimorfismos do gene LGALS3 (rs4644 e rs4652); AA do SOCS3 (rs4969170); CC do rs12979860 e TT do rs8099917 do IL-28B; AA do rs10212165, AA, AG e GG do rs3909582, CC e CT do rs9865082, AG e GG do rs9880018 e AA do rs9848283 do gene CLDN1; e CC do CCL5 (rs2280789) foram estatisticamente mais frequentes em indivíduos com fibrose cardíaca <15% quando comparados com o grupo com fibrose ≥15%. Diante do exposto concluimos que os polimorfismos analisados podem ser úteis como futuros biomarcadores para estadiamento e conduta terapêutica em pacientes com doença de Chagas.

ABSTRACT

Trypanosoma cruzi is an intracellular parasite and the agent that causes Chagas disease, which affects millions of people worldwide. Several factors and mediators are known to actively participate in the inflammation, fibrosis and tissue regeneration, which is triggered by T. cruzi within the host. The aim of this study was to evaluate the association of single nucleotide polymorphisms with clinical forms and rate of fibrosis in Chagas disease patients. The polymorphisms were analyzed by real-time PCR. The study consisted of 55 Chagas disease patients that were classified according to the clinical form of the disease, including 17 patients presenting the indeterminate form, 15 patients presenting the cardiac form without ventricular dysfunction and 23 patients presenting the cardiac form with ventricular dysfunction. The genotypes of CA of LGALS3 gene polymorphisms (rs4644 and rs4652); AG and GG of SOCS3 (rs4969170); CT and TT of IL-28B (rs12979860 and 8099917, respectively); AG, AG, CC, AG and AG of CLDN-1 (rs10212165, rs3909582, rs9865082, rs9880018 and rs9848283, respectively); and CC of CCL5 (rs2280789) were significantly more frequent in patients presenting the cardiac form compared to patients presenting the indeterminate form. Regarding the degree of fibrosis, the CC genotype of polymorphisms of the genes LGALS3 (rs4644 and rs4652); AA of SOCS3 (rs4969170); CC of rs12979860 and TT of rs8099917 of the IL-28B; AA of rs10212165 and AA, AG and GG of rs3909582, CC and CT of rs9865082, AG and GG of rs9880018 and AA of rs9848283 of the gene CLDN1; and CC of CCL5 (rs2280789) were statistically more frequent in patients presenting <15% cardiac fibrosis when compared to patients presenting fibrosis ≥15%. Taken together, our results suggest that the polymorphisms analyzed may be useful biomarkers for therapeutic management of patients with Chagas disease.