Analysis of TYK2 P1104A variant in a cohort of colombian patients with pulmonary tuberculosis

Abstract

Tuberculosis continues to be one of the main causes of death worldwide with around 10 million people infected annually, which is a direct problem for public health. Data that has accumulated over decades suggests that variability in human susceptibility to tuberculosis disease has a strong genetic component. Both primary and acquired immunodeficiencies (PID) are strongly related to broad infectious phenotypes that include the full range of diseases caused by the infectious agent Mycobacterium tuberculosis. Recently it was found that a PID found in up to 1/600 individuals of European descent, in fact a variant was found that affects the catalytic activity of TYK2 therefore selectively alters the immunity to IFN-g mediated by IL-23 while the responses to IL-10, IL-12, and IFN-a / b are intact. These PIDs are only expressed symptomatically after exposure to Mycobacterium tuberculosis. However, we hypothesize that homozygous for the P1104A variant or compound heterozygosity in this same TYK2 gene can confer a selective response, thus predisposing to TB. This study intends to 1. Identify the variant P1104A of the TYK2 gene in Colombian patients with pulmonary tuberculosis, 2. Identify other rare or common variants in the TYK2 gene in patients with pulmonary tuberculosis, 3. Correlating data from the Colombian population with what has been found in other populations.