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

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.