Evidence map›Paper›PMID 39591456›Full record

ArticlePLoS neglected tropical diseases2024

Influence of angiotensin II type 1 receptors and angiotensin-converting enzyme I/D gene polymorphisms on the progression of Chagas' heart disease in a Brazilian cohort: Impact of therapy on clinical outcomes.

Thayse do Espírito Santo Protásio da Silva, Lucia Elena Alvarado-Arnez, Angelica Martins Batista, Silvia Marinho Martins Alves, Gloria Melo, Cristina Veloso Carrazzone, Isabelle de Oliveira Moraes, Antonio G Pacheco, Camila Sarteschi, Milton Ozório Moraes and 2 more

Abstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Thayse do Espírito Santo Protásio da SilvaLaboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Lucia Elena Alvarado-ArnezLaboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Angelica Martins BatistaLaboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Silvia Marinho Martins AlvesLaboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Gloria MeloAmbulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, Pernambuco, Brazil.
Cristina Veloso CarrazzoneAmbulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, Pernambuco, Brazil.
Isabelle de Oliveira MoraesLaboratório de Hanseníase, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Antonio G PachecoPrograma de Computação Científica, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Camila SarteschiAmbulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, Pernambuco, Brazil.
Milton Ozório MoraesLaboratório de Hanseníase, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Wilson OliveiraAmbulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco (PROCAPE)/UPE, Recife, Pernambuco, Brazil.
Joseli Lannes-VieiraLaboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.ORCID 0000-0001-5503-6754

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chagas disease (CD), a neglected tropical disease, is caused by infection by the protozoan Trypanosoma cruzi. One-third of CD patients develop cardiac disease (CARD), an inflammatory and fibrotic process that may progress to heart failure associated with reduced left ventricular ejection fraction (LVEF). The determinants of CD progression are still uncertain. In non-infectious conditions, the angiotensin-converting enzyme (ACE) functional insertion (I)/deletion (D) and type 1 angiotensin II receptor (AT1R) +1166A>C gene polymorphisms have been linked to clinical outcomes. In a Brazilian cohort of 402 patients with positive serology for CD, in a case-control study we used PCR for genotyping the ACE rs4646994 I/D and AGTR1 rs5182C>T, rs275653 -119C>T, rs2131127A>G and rs5186 +1166A>C polymorphisms to evaluate association with CARD and progression to heart failure. Patients were classified as non-CARD (stage A; 109), and mild (stage B1; 161) or severe (stage C; 132) CARD. The groups were compared using unconditional logistic regression analysis and adjusted for non-genetic covariates (age, gender, and trypanocidal treatment). ACE II genotype appeared less frequent in C patients (15% in C vs 20% in B1 and 27% in A). After covariate adjustments, the ACE D allele showed a borderline association with susceptibility to severe CARD (C vs A: OR = 1.9; P = 0.08). AGTR1 +1166AC genotype showed a borderline association with protection against the progression and severity of CARD (C vs A: OR = 0.6; P = 0.09; C vs B1: OR = 0.6; P = 0.07; C vs A + B1: OR = 0.6; P = 0.05). However, adjustments for multiple comparisons showed no association of ACE I/D and AGTR1 polymorphisms with susceptibility and severity of CARD. The rs275653/rs2131127/rs5186/rs5182 T/A/C/T haplotype was protective against progression to the severe form of CARD (C vs B1: OR = 0.3; P = 0.03). Moreover, patients with ACE II and AGTR1 rs5186 +1166AC genotypes presented higher LVEF%. In C patients, TNF serum levels were higher in ACE D carriers than in II genotype. Although limited in number, a cross-sectional observation suggests that C-stage patients treated with benznidazole years prior to administration of ACE inhibitors/AT1R antagonists show reduced TNF serum levels and improved LVEF%. Therefore, variants of ACE and AGTR1 genes may influence the outcome of Chagas' heart disease and should be explored in precision medicine. Further, pharmacotherapies may improve immunological abnormality and clinical outcome in CD patients. Altogether, these data support prospective studies of this cohort and replication in other cohorts.

Indexed as

Chagas CardiomyopathyPeptidyl-Dipeptidase AReceptor, Angiotensin, Type 1AdultAgedBrazilCase-Control StudiesCohort StudiesDisease ProgressionFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideACE protein, humanAGTR1 protein, humanPeptidyl-Dipeptidase AReceptor, Angiotensin, Type 1

Identifiers

PMID39591456
PMCPMC11630595

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.