title: Genetic and functional role of TNF-alpha in the development Trypanosoma cruzi infection.
abstract: TNF-alpha plays an important role in trypanocidal mechanisms and is related to tissue injury. This cytokine has been detected in the heart of human chagasic patients where it is associated with tissue damage. This study investigated whether TNF-alpha levels and the presence of genetic polymorphisms are associated with the presence of T. cruzi infection and/or with the development of the cardiac form in chronic chagasic patients. Genomic DNA of 300 subjects from an endemic area was extracted and analyzed by PCR using specific primers. TNF-alpha was assayed in culture supernatants by ELISA. An association was observed between the absence of the TNF-238A allele and negative serology. Furthermore, seropositive individuals carrying the TNF-238A allele produced significantly higher TNF-alpha levels without stimulation (p=0.04) and after stimulation with LPS (p=0.007) and T. cruzi antigens (p=0.004). The present results suggest that the polymorphism at position -238 influences susceptibility to infection and that this allele is associated with higher TNF-alpha production in seropositive individuals.
authors.affiliation: Laboratory of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
authors.forename: Cristina Wide
authors.initials: CW
authors.lastname: Pissetti
authors.forename: Dalmo
authors.initials: D
authors.lastname: Correia
authors.forename: Rafael Faria
authors.initials: RF
authors.lastname: de Oliveira
authors.forename: Maurício Manoel
authors.initials: MM
authors.lastname: Llaguno
authors.forename: Marly Aparecida Spadotto
authors.initials: MA
authors.lastname: Balarin
authors.forename: Roseane Lopes
authors.initials: RL
authors.lastname: Silva-Grecco
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014355:Chagas Disease / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha