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Abstract
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.
Highlights
According to the World Health Organization and the Center for Disease Control and Prevention, 8 million people suffer from Chagas disease worldwide, mainly in Latin America
The three Tyrosine kinase 2 (TYK2) SNPs were in HWE in all the comparisons performed (P>0.01), and the genotyping success rate was over 95% for all analyzed genetic variants
In order to evaluate the association between TYK2 gene variants and susceptibility to T. cruzi infection, the allelic frequencies of seronegative and seropositive individuals were compared (Table 1)
Summary
According to the World Health Organization (http://www.who.int/chagas/en/) and the Center for Disease Control and Prevention (https://www.cdc.gov/parasites/chagas/), 8 million people suffer from Chagas disease worldwide, mainly in Latin America This disorder is caused by the infection with the protozoan parasite Trypanosoma cruzi [1, 2]. From a genetic point of view, different genes of the inflammatory immune response have shown statistically significant association with a differential risk to infection and to the development of chronic cardiomyopathy. It seems that the inflammatory immune response is the clue for controlling infection in early stages and to avoid the appearance of more severe symptoms. The evidence indicates that parasite persistence is fundamental for the onset of chronic Chagas cardiomyopathy
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