The IFNG rs1861494 single nucleotide polymorphism is associated with protection against tuberculosis disease in Argentina

Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The...

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Detalles Bibliográficos
Autores: Rolandelli, Agustin, Pellegrini, Joaquín Miguel, Amiano, Nicolás Oscar, Santilli, Maria Cecilia, Morelli, María Paula, Castello, Florencia Andrea, Tateosian, Nancy Liliana, Levi, Alberto, Casco, Nicolás, Palmero, Domingo, García, Verónica Edith
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/93889
Acceso en línea:http://hdl.handle.net/11336/93889
Access Level:acceso abierto
Palabra clave:INTERFERON GAMMA
MYCOBACTERIUM TUBERCULOSIS
RS1861494
SINGLE NUCLEOTIDE POLYMORPHISM
TUBERCULOSIS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 polymorphism (G→A) was reported to alter the binding of transcription factors to this region, influencing IFNG production. Using a case-control study, we found an association between the AA and AG genotypes and tuberculosis resistance (AA vs. GG: odds ratio (OR) = 0.235, p-value = 0.012; AG vs. GG: OR = 0.303, p-value = 0.044; AA vs. AG: OR = 0.776, p-value = 0.427; AA + AG vs. GG: OR = 0.270, p-value = 0.022). Moreover, Mtb-antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants (p-value = 0.034) and presented the greatest percentage of CD4+IFNG+ lymphocytes (p-value = 0.035), in comparison with GG carriers. No association between the polymorphism and clinical parameters of tuberculosis severity was detected. However, our findings indicate that the rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker of tuberculosis resistance in the Argentinean population.