FOXP3 gene polymorphisms are associated with indeterminate clinical form of Chagas disease

The forkhead box protein 3 (FOXP3) transcription factor is the main marker of regulatory T-cell (Treg) development and activation, a subpopulation involved in immune system regulation, self-tolerance, and protection against infections. We previously showed that Treg cells control the exacerbated immune response and morbidity in chronic Chagas disease, by modulating the cytokine environment and killing effector cells. Although FOXP3 gene polymorphisms have already been studied in several diseases, their role in Chagas disease is underreported. This study investigated FOXP3 gene polymorphism (rs3761548) in patients with Chronic Chagas disease and the association between FOXP3 polymorphisms (-3279 C/T and -3499 G/T) with clinical forms of the disease. We show that the -3499 G/T polymorphism of the heterozygous genotype (GT) is twice as prevalent in women with indeterminate clinical form (IND). Other analyses showed that the polymorphic allele (T + -3499 G/T) is high in women with IND, suggesting a protective role for this polymorphism. This pattern is associated with high frequency of FOXP3 in Treg cells in individuals with the IND form. Our results suggest that -3499 G/T polymorphism in the FOXP3 gene may play an important role in T. cruzi infection, contributing to control and the development of the IND clinical form.