The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina.

ROLANDELLI AGUSTIN; HERNÁNDEZ DEL PINO RODRIGO E; JOAQUIN PELLEGRINI; NANCY TATEOSIAN; AMIANO NICOLAS; DE LA BARRERA S; CASCO, NICOLÁS; GUTIERREZ MARISA; DOMINGO J. PALMERO; V.E. GARCIA

Scientific Reports

Nature

Año: 2016

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually.However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a humangenetic component. Here, we investigated the association of the rs2275913 SNP (G→A) from IL-17Aand tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functionalrelevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinicalparameters of the disease. We found an association between the AA genotype and tuberculosis resistance.Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) producedthe highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast,within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunologicalparameters and we evidenced an association between the AA genotype and clinical parameters of diseaseseverity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findingsdemonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protectionto active tuberculosis but related to higher disease severity in the Argentinean population