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

Autor: Brito, William Botelho de, Queiroz, Maria Alice Freitas, Amoras, Ednelza da Silva Gra?as, Lima, Sandra Souza, Conde, Simone Regina Souza da Silva, Santos, Eduardo Jos? Melo dos, Cayres-Vallinoto, Izaura Maria Vieira, Ishak, Ricardo, Vallinoto, Antonio Carlos Ros?rio
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Repositório Digital do Instituto Evandro Chagas (Patuá)
Instituto Evandro Chagas (IEC)
instacron:IEC
Popis: This work was supported by the Brazilian National Council for Sci-entific and Technological Development (CNPQ Nos. 480128/2013-8, 301869/2017-0 and 312979/2018-5) and by the Federal University of Par ?a (PROPESP/PAPQ/2020) Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. Federal University of Par?. Jo?o de Barros Barreto Hospital. Bel?m, Par?, Brazil / Federal University of Par?. Institute of Health Sciences. School of Medicine. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Human Genetics. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Virology. Bel?m, Par?, Brazil. The IFN-? and TGF-?1 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-? 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-?1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-?1 (p = 0.0400). IFN-? and TGF-?1 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-?1, which inhibits IFN-? production, contributing to the progression to cirrhosis
Databáze: OpenAIRE
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