TY - JOUR
T1 - Association of caspase-1 polymorphisms with chagas cardiomyopathy among individuals in Santa Cruz, Bolivia
AU - Fu, Katherine Yih Jia
AU - Zamudio, Roxana
AU - Frost, Jo Henderson
AU - Almuedo, Alex
AU - Steinberg, Hannah
AU - Clipman, Steven Joseph
AU - Duran, Gustavo
AU - Marcus, Rachel
AU - Crawford, Thomas
AU - Alyesh, Daniel
AU - Colanzi, Rony
AU - Flores, Jorge
AU - Gilman, Robert Hugh
AU - Bern, Caryn
N1 - Funding Information:
This work was supported by NIH R01-AI107028-01A1 and in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of California San Francisco. Katherine Fu is a Doris Duke International Clinical Research Fellow. The funding sources had no role in the study design, collection, analysis and interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication.
Publisher Copyright:
© 2017, Sociedade Brasileira de Medicina Tropical. All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Caspase-1
KW - Chagas cardiomyopathy
KW - Single nucleotide polymorphisms
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U2 - 10.1590/0037-8682-0015-2017
DO - 10.1590/0037-8682-0015-2017
M3 - Article
C2 - 28954073
AN - SCOPUS:85029924521
SN - 0037-8682
VL - 50
SP - 516
EP - 523
JO - Revista da Sociedade Brasileira de Medicina Tropical
JF - Revista da Sociedade Brasileira de Medicina Tropical
IS - 4
ER -