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Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil

Julio César Carranza1, Helder M S Valadares, Daniella A D'Avila

  • 1Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil.

International Journal for Parasitology
|June 9, 2009
PubMed

Insights

Mitochondrial gene analysis in Chagas disease patients did not differentiate between asymptomatic (indeterminate form) and severe (cardiomyopathy) outcomes. However, mutations in ND7 and ND4 genes reveal distinct Trypanosoma cruzi II sub-lineages.

Area of Science:

  • Molecular Biology
  • Parasitology
  • Genetics

Background:

  • Chagas disease, caused by Trypanosoma cruzi, presents an asymptomatic indeterminate form (IF) in most chronic patients, with a subset progressing to severe cardiac (CCHD) or gastrointestinal disease.
  • The factors influencing disease progression from IF to CCHD remain largely unknown, suggesting complex host-parasite-environment interactions.
  • Previous research identified a deletion in the ND7 gene of IF isolates, proposing its potential as a diagnostic marker.

Purpose of the Study:

  • To evaluate whether variations in the mitochondrial ND7 gene and other mitochondrial genes can distinguish Trypanosoma cruzi strains causing IF versus CCHD.
  • To analyze the genetic diversity of Trypanosoma cruzi isolates from patients in Southeast Brazil with defined pathologies.
  • To investigate the evolutionary relationships and sub-lineages within Trypanosoma cruzi based on mitochondrial gene structure.

Main Methods:

  • Analysis of the ND7 gene structure in Trypanosoma cruzi isolates from 75 patients with known Chagas disease clinical outcomes.
  • Examination of additional mitochondrial genes (ND4/CR4, COIII, COII) to assess their utility in parasite clustering.
  • Genotyping of Trypanosoma cruzi isolates to determine their discrete typing units (DTUs) and haplogroups.

Main Results:

  • Mitochondrial gene analysis, including ND7, did not differentiate between parasite populations associated with IF or CCHD.
  • The majority of analyzed isolates belonged to the T. cruzi II (DTU IIb) genotype, contrasting with hybrid DTU IId prevalence in other South American countries.
  • Mutations in ND7 and ND4 genes suggest distinct ancestral origins and at least three mitochondrial sub-lineages within the T. cruzi II cluster.

Conclusions:

  • Maxicircle genes are not suitable for discriminating between Trypanosoma cruzi strains that cause indeterminate versus severe Chagas disease.
  • The genetic makeup of Trypanosoma cruzi isolates in Southeast Brazil differs from that observed in Bolivia, Chile, and Argentina.
  • Accumulated mutations in mitochondrial complex I genes support the hypothesis of reduced complex I activity in Trypanosoma cruzi.

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