Katherine Yih-Jia Fu1, Roxana Zamudio2, Jo Henderson-Frost3, Alex Almuedo4, Hannah Steinberg5, Steven Joseph Clipman5, Gustavo Duran6, Rachel Marcus7, Thomas Crawford8, Daniel Alyesh8, Rony Colanzi9, Jorge Flores6, Robert Hugh Gilman5, Caryn Bern10. 1. Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America. 2. Department of Genetics, University of Leicester, Leicester, United Kingdom. 3. Massachusetts General Hospital, Boston, Massachusetts, United States of America. 4. Fundació Hospital de Granollers, Granollers, Barcelona, Spain. 5. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. 6. Hospital San Juan de Dios, Santa Cruz de la Sierra, Bolivia. 7. MedStar Washington Hospital Center, Washington, District of Columbia, United States of America. 8. Division of Cardiology, University of Michigan, Ann Arbor, Michigan, United States of America. 9. Hospital Japones, Santa Cruz de la Sierra, Bolivia. 10. Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, California, United States of America.
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.
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.
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