A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18 , IL17A , and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease
Chagas disease caused by ( ) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between , , , or polymorphism profiles and cardiomyopathy or par...
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| Published in: | Frontiers in immunology Vol. 11; p. 521409 |
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| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
22-10-2020
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Chagas disease caused by
(
) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between
,
,
, or
polymorphism profiles and cardiomyopathy or
parasitemia, as well as the impact of HIV infection on cardiopathy.
Two hundred twenty-six patients and 90 control individuals were analyzed.
rs1143627 T>C,
rs1800795 C>G,
rs2275913 G>A,
rs187238 C>G, and
rs1946518 C>A SNVs were analyzed by real-time PCR and
parasitemia by PCR.
Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The
rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between
rs2275913 AA and
s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively).
rs1946518 AA and
rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for
rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively).
Our data support a protective role of
AA,
AA, and
TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the
CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies. |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology Reviewed by: Thomas Jacobs, Bernhard Nocht Institute for Tropical Medicine (BMITM), Germany; Fabrício C. Dias, University of São Paulo, Brazil; Celso Teixeira Mendes-Junior, University of São Paulo, Brazil Edited by: David Courtin, Institut de recherche pour le développement (IRD), France These authors have contributed equally to this work |
| ISSN: | 1664-3224 1664-3224 |
| DOI: | 10.3389/fimmu.2020.521409 |