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Libro de resúmenes FAIC - The IL-17 RS2275913 single nucleotide polymorphism (SNP) is associated with human tuberculosis susceptibility in Argentina.
Congreso
Authorship:
Rolandelli Agustin ; Rodrigo Hernandez Del Pino ; Guadalupe Ines Alvarez ; Joaquin Pellegrini ; N. Tateosian ; Amiano Nicolas ; Palmero DJ ; Nicolás Casco ; Gutierrez Marisa ; Pasquineli, V ; García VDate:
2015Publishing House and Editing Place:
N/ASummary *
Background. Interleukin 17A (IL-17) plays an important role in host-pathogen interaction during Mycobacterium tuberculosis (Mtb) infection. Genetic variations in IL-17 gene may affect the immune response against this bacterium. The SNPrs2275913 (g/a) is the most studied nucleotide substitution in IL-17A gene, but only one study reported the association of this SNP with tuberculosis susceptibility in a Spanish population. Here we investigated the relationship between rs2275913 SNP and tuberculosis susceptibility in Argentina and evaluated the functional implications of the substitution. Methods. 146 tuberculosis patients (TB) and 164 healthy donors(HD) were genotyped by ARMS-PCR. IFN-gamma and IL-17A levels were analyzed by ELISA in plasma and supernatants from peripheral blood mononuclear cells (PBMCs) stimulated with a Mtb lysate. Results. Significant differences in the allelic and genotypic(p<0.001) distribution of the rs2275913 SNP were found between TB and HD. Moreover, AA or GA individuals showed a marked lower association with tuberculosis development as compared with GG subjects (OR AAvsGG=0.27, OR GAvsGG=0.48;p<0.01). Additionally, higher IL-17 levels were detected in plasma(p<0.01HD; p<0.05TB) and PBMCs supernatants (p<0.05HD;p<0.05TB) of AA individuals as compared to GG subjects. Furthermore, higher levels of IFN-gamma were detected insupernatants of AA and GA HD compared to GG donors (p<0.01).In contrast, in TB, significant higher IFN-gamma levels were detected in supernatants of GG and GA subjects (p<0.05). Thus,the IL-17 genotypes might differentially regulate the cytokine microenvironment. Conclusions. Our results suggest that AA and GA genotypes couldbe important protection markers during active tuberculosis development in Argentina. Information provided by the agent in SIGEVAKey Words
SNPIL-17TUBERCULOSIS