Association of caspase-1 polymorphisms with chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Katherine Yih Jia Fu, Roxana Zamudio, Jo Henderson Frost, Alex Almuedo, Hannah Steinberg, Steven Joseph Clipman, Gustavo Duran, Rachel Marcus, Thomas Crawford, Daniel Alyesh, Rony Colanzi, Jorge Flores, Robert Hugh Gilman, Caryn Bern

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20–30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy. Methods: We recruited infected (Tc+, n=149) and uninfected (Tc−, n=87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex. Results: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR)=−2.18, p=0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR=−2.64, p=0.064). Conclusions: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

Original languageEnglish (US)
Pages (from-to)516-523
Number of pages8
JournalRevista da Sociedade Brasileira de Medicina Tropical
Volume50
Issue number4
DOIs
StatePublished - Jul 1 2017

Keywords

  • Caspase-1
  • Chagas cardiomyopathy
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Parasitology
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Association of caspase-1 polymorphisms with chagas cardiomyopathy among individuals in Santa Cruz, Bolivia'. Together they form a unique fingerprint.

Cite this