TGF-β Polymorphisms Are a Risk Factor for Chagas Disease.

Area of Science:

• Immunogenetics
• Molecular Epidemiology
• Parasitic Diseases

Background:

• Transforming growth factor beta 1 (TGF-β1) plays a key role in Chagas disease pathogenesis.
• Elevated TGF-β1 serum levels are associated with poorer clinical outcomes in patients.
• Genetic variations, specifically gene polymorphisms, can influence cytokine production and disease susceptibility.

Purpose of the Study:

• To investigate the association between TGFB1 gene polymorphisms and susceptibility to Chagas disease in a Brazilian population.
• To determine if specific TGFB1 polymorphisms are linked to the severity of Chagas disease (indeterminate vs. cardiac forms).

Main Methods:

• Genotyping of five single-nucleotide polymorphisms (SNPs) in the TGFB1 gene: -800 G>A, -509 C>T, +10 T>C, +25 G>C, and +263 C>T.
• Analysis of genotype frequencies in 152 Chagas disease patients (53 indeterminate, 99 cardiac) and 48 non-infected controls from Brazil.

Main Results:

• The CT and TT genotypes at the -509 C>T position of the TGFB1 gene were significantly more frequent in Chagas disease patients compared to controls.
• The TC and CC genotypes at codon +10 T>C of the TGFB1 gene were also more prevalent in patients with Chagas disease than in non-infected individuals.
• No significant association was found between the studied TGFB1 polymorphisms and the clinical form (indeterminate or cardiac) of Chagas disease.

Conclusions:

• The -509 C>T and +10 T>C polymorphisms in the TGFB1 gene are associated with increased susceptibility to Chagas disease in the Brazilian population.
• These findings highlight the role of genetic factors in Chagas disease risk, independent of disease progression to cardiac complications.