Comprehensive analysis of three TYK2 gene variants in the susceptibility to Chagas disease infection and cardiomyopathy

Tyrosine kinase 2 (TYK2) is a member of the Janus kinases family implicated in the signal transduction of type I interferons and several interleukins. It has been described that genetic mutations within TYK2 lead to multiple deleterious effects in the immune response. In this work, we have analyzed three functional independent variants from the frequency spectrum on the TYK2 gene (common and low-frequency variants) suggested to reduce the function of the gene in mediating cytokine signaling and the susceptibility to infections by Trypanosoma cruzi and/or the development of Chagas cardiomyopathy in the Colombian population. A total of 1,323 individuals from a Colombian endemic region for Chagas disease were enrolled in the study. They were classified as seronegative (n = 445), seropositive asymptomatic (n = 336), and chronic Chagas Cardiomyopathy subjects (n = 542). DNA samples were genotyped using TaqMan probes. Our results showed no statistically significant differences between the allelic frequencies of the three analyzed variants when seropositive and seronegative individuals were compared, therefore these variants were not associated with susceptibility to Chagas disease. Moreover, when Chagas cardiomyopathy patients were compared to asymptomatic patients, no significant associations were found. Previous reports highlighted the association of this gene in immune-related disorders under an autoimmunity context, but not predisposing patients to infectious diseases, which is consistent with our findings. Therefore, according to our results, TYK2 gene variants do not seem to play an important role in Chagas disease susceptibility and/or chronic Chagas cardiomyopathy.This work has received support from the grant nº 1102-519-29071 from the Departamento Administrativo de Ciencia, Tecnología e Innovación, Colciencias (http://www.colciencias.gov.co), and the Universidad Industrial de Santander, Bucaramanga, Colombia, CIG. This study is part of the “Red Iberoamericana de Medicina Genómica en Enfermedad de Chagas” (RIMGECH-217RT0524). MAH is recipient of a Juan de la Cierva fellowship (FJCI-2015-24028) and FDC is recipient of a grant from the Ramon y Cajal programme (RYC-2014-16458), both from the Spanish Ministry of Economy, Industry and Competitiveness