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

MedStar author(s):
Citation: Revista Da Sociedade Brasileira de Medicina Tropical. 50(4):516-523, 2017 Jul-AugPMID: 28954073Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Caspase 1/ge [Genetics] | *Chagas Cardiomyopathy/en [Enzymology] | *Polymorphism, Genetic/ge [Genetics] | Aged | Bolivia | Case-Control Studies | Female | Genotype | Humans | Male | Middle AgedYear: 2017ISSN:
  • 0037-8682
Name of journal: Revista da Sociedade Brasileira de Medicina TropicalAbstract: 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).All authors: Almuedo A, Alyesh D, Bern C, Clipman SJ, Colanzi R, Crawford T, Duran G, Flores J, Fu KY, Gilman RH, Henderson-Frost J, Marcus R, Steinberg H, Zamudio RFiscal year: FY2018Digital Object Identifier: Date added to catalog: 2017-09-29
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Journal Article MedStar Authors Catalog Article 28954073 Available 28954073

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).

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