Chagas’ disease, caused by Trypanosoma cruzi, is an important parasitic disease in Latin America, affecting more than 8 millions of people. The chronic phase is characterized by commitment of heart or digestive organs and the reason for the development of one clinical form or another is not well known. It is speculated that host and parasite genetic characteristics contribute for it. LT-α is an inflammatory cytokine, important in the organization and maintenance of the inflammatory process by stimulating adhesion molecules, such as VCAM, ICAM and E-selectin. Polymorphism on LT-α gene, position +252, were analyzed on subjects (n= 295) from an endemic area for Chagas’ disease grouped according to serology for T. cruzi and with clinical form (cardiac or indeterminate forms).Expression of LT-α was evaluated in culture supernatants and by flow cytometry. Presence of G allele was significantly more frequent in patients with heart commitment (cardiac form) (p=0.016, OR=2.4). Patients with cardiac form produced significantly more LT-α than individuals with the indeterminate form. Furthermore, infected individuals with G allele produced significantly higher levels of LT-α than those without G allele. CD8+ T lymphocytes were the major source of LT-α in basal condition and after stimulation with specific antigens. This study presents genetic and biological evidence for a role of LT-α in the development of cardiac form of Chagas’ disease.

BackgroundObesity contributes to several cardiometabolic diseases, such as dyslipidemia, as a result of an unhealthy lifestyle and genetic factors. The methylation profile of genes involved in appetite control and metabolism, such as LEP (leptin) and POMC (proopiomelanocortin) and altered lipid levels can contribute to obesity, and these epigenetic changes have been associated with the effects of diet composition. The objective of this study was to evaluate the methylation levels of LEP and POMC genes and lipid profile values after intervention with dietary folate and hazelnut oil in overweight women.MethodsDouble-blind, placebo, controlled intervention study with 40 overweight adult women. Participants were randomized into four groups for 8 weeks: G1, 300 g of vegetables and 191 µg / day of folate and hazelnut oil; G2, 300 g of vegetables and 191 µg / day of folate and placebo; G3, 300 g of vegetables and 94 µg / day of folate and hazelnut oil; G4, the individuals were only accompanied. In addition to the levels of methylation, food consumption, anthropometric measurements, biochemical variables of lipid profile were evaluated.ResultsAfter the intervention, the participants presented reduction in the methylation levels of the studied genes in the three intervention groups in the LEP gene: G1 (p = 0.00), G2 (p = 0.00) and G3 (p = 0.00); in the POMC gene: G1 (p = 0.01), G2 (p = 0.02) and G3 (p = 0.01), and in the lipid profile, G1 reduced the levels of LDL-c (p = 0.04), HDL-c (p = 0.00) and Triglycerides (p = 0.04); in G3 there was a reduction in total cholesterol levels (p = 0.00), LDL-c (p = 0.00) and HDL-c (p = 0.00), and in G4 there was a reduction in total cholesterol values (p = 0.00), LDL-c (p = 0.00), HDL-c (p = 0.00) and triglycerides (p = 0.00), and also, an association in G2 between the POMC methylation levels with triglycerides (p = 0.00).ConclusionThe study provided evidence of a normocaloric intervention with dietary folate and hazelnut oil supplementation on the methylation levels of LEP and POMC genes and the role they can play in lipid metabolism.Trial registrationISRCTN, NCT04523532. Registered 21 August 2020, https://clinicaltrials.gov/ct2/show/NCT04523532