IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-gamma 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-gamma 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-gamma 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-gamma gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). Leishmania-induced IFN-gamma 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-gamma than TA/TT genotypes. In mucosal cases, high and low IFN-gamma producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.


CONCLUSIONS
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-alpha and IL-10 are also involved thus interfering with IFN-gamma secretion.
Matos
Guilherme Inocêncio
GI
Laboratório de Hanseníase, Departamento de Micobacterioses, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. gmatos@ioc.fiocruz.br <gmatos@ioc.fiocruz.br>
Covas
Claudia de J Fernandes
Cde J
Bittar
Rita de Cássia
Rde C
Gomes-Silva
Adriano
A
Marques
Fabiana
F
Maniero
Viviane C
VC
Amato
Valdir S
VS
Oliveira-Neto
Manoel P
MP
Mattos
Marise da Silva
Mda S
Pirmez
Claude
C
Sampaio
Elizabeth P
EP
Moraes
Milton O
MO
Da-Cruz
Alda Maria
AM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001938:Brazil; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D007891:Leishmania / Q000276:immunology / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D000953:Antigens, Protozoan; D007371:Interferon-gamma