The TGFB1-509C/T polymorphism and elevated TGF-beta 1 levels are associated with chronic hepatitis C and cirrhosis

• Autor(a) principal: Brito, William Botelho de
• Data de Publicação: 2020
• Outros Autores: Queiroz, Maria Alice Freitas, Amoras, Ednelza da Silva Graça, Lima, Sandra Souza, Conde, Simone Regina Souza da Silva, Santos, Eduardo José Melo dos, Cayres-Vallinoto, Izaura Maria Vieira, Ishak, Ricardo, Vallinoto, Antonio Carlos Rosário
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/4229
• topic: Hepatite C Crônica / patologia; Hepacivirus; Cirrose Hepática; Fator de Crescimento Transformador alfa; Interferon gama; Volume Plasmático

The IFN-γ and TGF-β1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-β1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-β1 (p = 0.0400). IFN-γ and TGF-β1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-β1, which inhibits IFN-γ production, contributing to the progression to cirrhosis