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Open Access Research article

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

Guilherme Inocêncio Matos2, Claudia de J Fernandes Covas1, Rita de Cássia Bittar1, Adriano Gomes-Silva1, Fabiana Marques3, Viviane C Maniero2, Valdir S Amato4, Manoel P Oliveira-Neto5, Marise da Silva Mattos5, Claude Pirmez3, Elizabeth P Sampaio2, Milton O Moraes2 and Alda Maria Da-Cruz1*

Author Affiliations

1 Laboratório de Imunoparasitologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil

2 Laboratório de Hanseníase, Departamento de Micobacterioses, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil

3 Laboratório de Imunopatologia, Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil

4 Ambulatório de Leishmanioses, Divisão de Clínica de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

5 Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil

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BMC Infectious Diseases 2007, 7:33  doi:10.1186/1471-2334-7-33

Published: 24 April 2007

Abstract

Background

Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ in vitro.

Methods

Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.

Results

There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.

Conclusion

Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.