The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina

• Published in: Genes 2018-01, Vol.9 (1), p.46
• Main Authors: Rolandelli, Agustín, Pellegrini, Joaquín M, Amiano, Nicolás O, Santilli, María C, Morelli, María P, Castello, Florencia A, Tateosian, Nancy L, Levi, Alberto, Casco, Nicolás, Palmero, Domingo J, García, Verónica E
• Format: Article
• Language: English
• Subjects: CD4 antigen; Cell culture; Gene polymorphism; Leukocytes (mononuclear); Lymphocytes; Peripheral blood mononuclear cells; Population genetics; Single-nucleotide polymorphism; Transcription factors; Tuberculosis; γ-Interferon
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes9010046

Interferon gamma (IFNG) plays a key role during ( ) 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 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, -value = 0.012; AG vs. GG: OR = 0.303, -value = 0.044; AA vs. AG: OR = 0.776, -value = 0.427; AA + AG vs. GG: OR = 0.270, -value = 0.022). Moreover, -antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants ( -value = 0.034) and presented the greatest percentage of CD4⁺IFNG⁺ lymphocytes ( -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.