Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

Rev Soc Bras Med Trop. 2020:53:e20190488. doi: 10.1590/0037-8682-0488-2019. Epub 2020 Jul 3.

Abstract

Introduction: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy.

Methods: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment.

Results: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04).

Conclusions: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors
  • Brazil
  • Case-Control Studies
  • Chagas Disease / genetics*
  • Chagas Disease / physiopathology
  • Cohort Studies
  • Disease Progression
  • Female
  • Genotype
  • Heart Failure / genetics
  • Heart Failure / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic / genetics*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Peptidyl-Dipeptidase A