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Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil

Alvarado-Arnez, Lucia Elena ; Batista, Angelica Martins ; Alves, Silvia Marinho ; Melo, Gloria ; Lorena, Virgínia Maria Barros de ; Cardoso, Cynthia C ; Pereira, Isabela Resende ; Carrazzone, Cristina ; Pacheco, Antonio G ; Oliveira, Jr, Wilson ; Moraes, Milton Ozório ; Lannes-Vieira, Joseli

Memórias do Instituto Oswaldo Cruz, 2018-05, Vol.113 (6), p.e170489-e170489 [Periódico revisado por pares]

Brazil: Instituto Oswaldo Cruz, Ministério da Saúde

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Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil
Autor: Alvarado-Arnez, Lucia Elena ; Batista, Angelica Martins ; Alves, Silvia Marinho ; Melo, Gloria ; Lorena, Virgínia Maria Barros de ; Cardoso, Cynthia C ; Pereira, Isabela Resende ; Carrazzone, Cristina ; Pacheco, Antonio G ; Oliveira, Jr, Wilson ; Moraes, Milton Ozório ; Lannes-Vieira, Joseli
Assuntos: Brazil ; cardiomyopathy ; Case-Control Studies ; Chagas Cardiomyopathy - complications ; Chagas Cardiomyopathy - genetics ; Chagas Cardiomyopathy - immunology ; Chagas disease ; cytokines ; Cytokines - genetics ; Female ; gene polymorphism ; Genetic Predisposition to Disease ; Humans ; Interferon-gamma - genetics ; Male ; meta-analysis ; Middle Aged ; Original ; PARASITOLOGY ; Polymorphism, Single Nucleotide - genetics ; Prognosis ; Receptors, Tumor Necrosis Factor, Type I - genetics ; Receptors, Tumor Necrosis Factor, Type II - genetics ; Severity of Illness Index ; Socioeconomic Factors ; Transforming Growth Factor beta - genetics ; TROPICAL MEDICINE ; Trypanosoma cruzi ; Tumor Necrosis Factor-alpha - genetics
É parte de: Memórias do Instituto Oswaldo Cruz, 2018-05, Vol.113 (6), p.e170489-e170489
Notas: ObjectType-Article-2
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LEAA's current address: Franz Tamayo University/UNIFRANZ (Cochabamba, Bolivia).
JLV, MOM and WOJr - Conception of the idea; JLV, MOM, WOJr, CC, LEAA and AMB - experimental design; LEAA, AMB, SMA, GM, VMBL and IRP - performing experiments; LEAA, AMB, SMA, GM, CCC, IRP, WOJr, MOM, AGP and JLV - data analysis; LEAA, AMB, MOM and JLV - writing.
AUTHORS' CONTRIBUTION
LEA-A, AMB and SMA contributed equally to this work.
Descrição: The severity of chronic chagasic cardiomyopathy (CCC), the most frequent clinical outcome of Chagas disease (CD), has been associated with cytokine-enriched heart tissue inflammation, and high serum levels of transforming growth factor (TGFβ), interferon-gamma (IFNγ), and tumour necrosis factor (TNF). Conversely, increased interleukin (IL)-10 serum concentrations have been associated with asymptomatic CD. Cytokines and cytokine-related gene polymorphisms may control cytokine expression and have been proposed to contribute to CCC outcomes. We evaluated the association of 13 cytokine-related genes (TGFB: rs8179181, rs8105161, rs1800469; IL10: rs1800890, rs1800871, rs1800896; IFNG: rs2430561; TNF: rs1800629; BAT1: rs3853601; LTA: rs909253, rs2239704; TNFR1: rs767455; TNFR2: rs1061624) with risk and progression of CCC. Four hundred and six seropositive patients from CD endemic areas in the state of Pernambuco, north-eastern Brazil, were classified as non-cardiopathic (A, 110) or cardiopathic (mild, B1, 163; severe, C, 133). We found no evidence of TGFB, IL10, TNF, or TNFR1/2 gene polymorphisms associated with CCC risk or progression. Only BAT1 rs3853601 -22G carriers (B1 vs. C: OR = 0.5; p-value = 0.03) and IFNG rs2430561 +874AT (A vs. C: OR = 0.7; p-value = 0.03; A vs. B1+C: OR = 0.8; p-value = 0.02) showed a significant association with protection from cardiopathy in a logistic regression analysis with adjustment for gender and ethnicity; however, the association disappeared after performing adjustment for multiple testing. A systematic review of TNF rs1800629 -308G>A publications included five studies for meta-analysis (534 CCC and 472 asymptomatic patients) and showed no consensus in pooled odds ratio (OR) estimates for A allele or A carriers (OR = 1.4 and 1.5; p-values = 0.14 and 0.15, respectively). In CD patients, TNF serum levels were increased, but not affected by the TNF rs1800629 -308A allele. Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes.
Editor: Brazil: Instituto Oswaldo Cruz, Ministério da Saúde
Idioma: Inglês;Português

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Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil

Alvarado-Arnez, Lucia Elena ; Batista, Angelica Martins ; Alves, Silvia Marinho ; Melo, Gloria ; Lorena, Virgínia Maria Barros de ; Cardoso, Cynthia C ; Pereira, Isabela Resende ; Carrazzone, Cristina ; Pacheco, Antonio G ; Oliveira, Jr, Wilson ; Moraes, Milton Ozório ; Lannes-Vieira, Joseli

Brazil: Instituto Oswaldo Cruz, Ministério da Saúde

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