Association between the lymphotoxin-alpha gene polymorphism and chagasic cardiopathy.

Abstract

Lymphotoxin-alpha (LT-alpha or LTA) is an inflammatory cytokine that is involved in the organization and maintenance of the inflammatory process and in the arrangement of cells at the site of inflammation. These features suggest an important role in the development of chronic Chagas' disease, especially the cardiac form. The objective of this study was to evaluate LT-alpha genetics and its biological role in chronic Chagas' disease. A total of 284 subjects were studied. The LT-alpha single-nucleotide polymorphism (+252) was analyzed by the polymerase chain reaction-restriction fragment length polymorphism and expression by enzyme-linked immunosorbent assay in culture supernatants and in individual T lymphocytes by flow cytometry. The risk of developing the cardiac form was 2.8 times higher among carriers of genotype GG and 2.4 times among carriers of genotype GA when compared to subjects carrying genotype AA. Seropositive subjects carrying the G allele produced significantly higher levels of LT-alpha. The cytokine was mainly expressed by CD8(+) T lymphocytes in the absence of any stimulus and after stimulation with the Trypanosoma cruzi antigen. This study provides genetic and biological evidence for an important role of LT-alpha in the development of the cardiac form of Chagas' disease.

• Authors: Cristina Wide Pissetti, Rafael Faria de Oliveira, Dalmo Correia, Gabriel Antonio Nogueira Nascentes, Mauricio Manoel Llaguno, Virmondes Rodrigues Jr
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 33 Issue 3 Pg. 130-5 (Mar 2013) ISSN: 1557-7465 [Electronic] United States
• PMID: 23289732 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Lymphotoxin-alpha

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Protozoan (immunology)
• CD8-Positive T-Lymphocytes (immunology, parasitology)
• Case-Control Studies
• Chagas Cardiomyopathy (epidemiology, genetics, immunology, parasitology)
• Female
• Gene Expression Regulation (genetics, immunology)
• Humans
• Lymphotoxin-alpha (genetics, immunology)
• Male
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Trypanosoma cruzi (immunology)