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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Medicina Tropical (SBMT)
• Series: Revista da Sociedade Brasileira de Medicina Tropical
• Subjects: Chagas cardiomyopathy; Single nucleotide polymorphisms; Caspase-1
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400516&lng=en&tlng=en

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.