Transforming growth factor beta 1 (TGFbeta1) gene polymorphisms and Chagas disease susceptibility in Peruvian and Colombian patients.

Susceptibility to Chagas disease infections and its clinical manifestations may be influenced by host genetic factors. Among cytokines, the multifunctional transforming growth factor beta 1 (TGFbeta1), plays a major role in the establishment and pathogenesis of Trypanosoma cruzi infection, the etiological agent of Chagas disease. Several single-nucleotide polymorphisms (SNP) in the TGFbeta1 gene that may affect cytokine production have been described. We investigated, by PCR methods, five SNP in the TGFbeta1 gene of known or suggested functional significance (-988 C/A; -800 G/A; -509 C/T; 10 T/C and 263 C/T) in 347 seropositive (asymptomatic, n=175; cardiomyopathic, n=172) and 279 seronegative unrelated individuals from a Peruvian and a Colombian population where T. cruzi is highly endemic. We found a significant difference in the distribution of the TGFbeta1 10T and 10C alleles between patients and healthy controls in both cohorts, analyzed independently and combined. The frequency of the high TGFbeta1 producer genotype 10 C/C was increased in the patients groups of both populations. Our data suggests that TGFbeta1 genetic polymorphisms at codon 10 may be involved in a differential susceptibility to T. cruzi infection in these South American samples.