DOI: 10.5061/dryad.wstqjq2hn
title: A specific IL6 polymorphic genotype modulates the risk of T. cruzi parasitemia while IL18, IL17A and IL1B variant profiles and HIV infection protect against cardiomyopathy in Chagas disease

description: Background: Chagas disease caused by Trypanosoma cruzi (T. cruzi)
 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 IL1B, IL6, IL17A or IL18 polymorphism profiles and cardiomyopathy
 or T. cruzi parasitemia, as well as the impact of HIV infection on
 cardiopathy. Methods: 206 patients and 90 control individuals
 were analyzed. IL1B rs1143627 T&gt;C, IL6 rs1800795 C&gt;G, IL17A
 rs2275913 G&gt;A, IL18 rs187238 C&gt;G, and IL18 rs1946518
 C&gt;A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by
 PCR. Results: Our data revealed association between a cytokine
 gene polymorphism and parasitemia never previously reported. The IL6
 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 IL17A rs2275913 AA and IL18 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). IL18 rs1946518 AA and
 IL1B 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) &lt;45%
 for IL18 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&lt;0.001) and LVEF&lt;45%
 (OR=0.03, 95% CI 0.00‐0.25, P=0.001). Digestive involvement was negatively
 associated with NYHA ≥2 and LVEF&lt;45% (OR=0.20, 95% CI 0.09‐0.47,
 P&lt;0.001; and OR=0.24, 95% CI 0.09-0.62, P=0.004, respectively).
 Conclusions: Our data support a protective role of IL17A AA, IL18
 AA and IL1B TC genotypes against development/progression of cardiomyopathy
 and a modulatory effect of the IL6 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 HAART, attenuating a Th1-mediated response
 in the myocardium. This proposed hypothesis requires confirmation,
 however, in larger and more comprehensive future studies.
description: Our cohort included 206 patients with Chagas disease: 78 from the
 Heart Institute of Hospital das Clínicas da Faculdade de Medicina,
 University of São Paulo (HCFMUSP), and 129 from the Infectious Diseases
 Division of HCFMUSP, 49 of whom with HIV co-infection. These 49 cases were
 followed at Serviço de Extensão e Atendimento aos Pacientes com Infecção
 por HIV/Aids of the same Division. All participants were adults. The
 diagnosis of trypanosomiasis was based on the 2nd Brazilian Guidelines for
 Chagas Diseases (1). Two positive tests of the following ones, therefore,
 were used to establish the diagnosis: ELISA - enzyme linked immunosorbent
 assay, indirect immunofluorescence, and hemagglutination (39). All
 patients from the Infectious Diseases Division with positive epidemiology
 were sent to the HIV/Aids Clinic, where HIV infection was confirmed by
 ELISA and immunoblot (31). Patients from the Heart Institute were tested
 for HIV as previously described (31). When included in the current
 protocol, 26 of the 49 HIV patients were not on regular HAART therapy or
 had therapeutic failure due to antiretroviral resistance (3 patients). In
 23 of them, the median viral load was 14,000 (2,618-100,000) DNA viral
 copies/µL while the median CD4 count was 340 (93-510) cells/mm3. Data from
 23 patients under HAART for 1 to &gt;5 years showed a median viral
 load of 0.0 (0.0-0.0) DNA viral copies/ µL. In these 23 patients, the
 median CD4 count was 631 (439-715) cells/ mm3. The
 patients underwent electrocardiography, echocardiography, and thorax,
 esophagus, and colon radiological examinations, being then classified
 within one of the clinical forms of Chagas disease (1). Individuals
 without signs and symptoms and with no alteration in the mentioned tests
 were classified as having the indeterminate form (n=51), patients with
 abnormalities suggestive of Chagas disease on electrocardiography or on
 dynamic electrocardiography and without digestive involvement as with the
 cardiac form (n=96), the cases with abnormal findings on esophagus and/or
 colon without Chagas cardiac manifestation as presenting the digestive
 form (n=32). Twenty seven patients presented both digestive and cardiac
 alterations, constituting the cardiodigestive group. Cardiac involvement
 was detected in 123 patients (cardiac and cardiac/digestive forms) while
 heart disease was not identified in 83 patients, a group composed of
 individuals with the indeterminate and digestive forms.
 Patients with cardiomyopathy were evaluated for heart failure
 according to the New York Heart Association (NYHA) classification (40) and
 placed in one of two groups based on the left ventricular ejection
 fraction (LVEF) yielded by echocardiography: ≥45% or
 &lt;45%.
description: The dataset is in xlsx format. It contains the patients
 demographics, clinical, laboratorial and echocardiogram data and the
 genotypes for  IL1B, IL6, IL17A and IL18 polymorphisms.