Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia
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 re...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Medicina Tropical (SBMT)
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| Series: | Revista da Sociedade Brasileira de Medicina Tropical |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400516&lng=en&tlng=en |
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| author | 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 |
| author_facet | 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 |
| author_sort | Katherine Yih-Jia Fu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T19:24:06Z |
| format | Article |
| id | doaj.art-ff05e2c39877408c87eacfa2d2719497 |
| institution | Directory Open Access Journal |
| issn | 1678-9849 |
| language | English |
| last_indexed | 2024-12-12T19:24:06Z |
| publisher | Sociedade Brasileira de Medicina Tropical (SBMT) |
| record_format | Article |
| series | Revista da Sociedade Brasileira de Medicina Tropical |
| spelling | doaj.art-ff05e2c39877408c87eacfa2d27194972022-12-22T00:14:33ZengSociedade Brasileira de Medicina Tropical (SBMT)Revista da Sociedade Brasileira de Medicina Tropical1678-984950451652310.1590/0037-8682-0015-2017S0037-86822017000400516Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, BoliviaKatherine Yih-Jia FuRoxana ZamudioJo Henderson-FrostAlex AlmuedoHannah SteinbergSteven Joseph ClipmanGustavo DuranRachel MarcusThomas CrawfordDaniel AlyeshRony ColanziJorge FloresRobert Hugh GilmanCaryn BernAbstract 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400516&lng=en&tlng=enChagas cardiomyopathySingle nucleotide polymorphismsCaspase-1 |
| spellingShingle | 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 Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia Revista da Sociedade Brasileira de Medicina Tropical Chagas cardiomyopathy Single nucleotide polymorphisms Caspase-1 |
| title | Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia |
| title_full | Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia |
| title_fullStr | Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia |
| title_full_unstemmed | Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia |
| title_short | Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia |
| title_sort | association of caspase 1 polymorphisms with chagas cardiomyopathy among individuals in santa cruz bolivia |
| topic | Chagas cardiomyopathy Single nucleotide polymorphisms Caspase-1 |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400516&lng=en&tlng=en |
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