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Fibrogenic Polymorphisms (TGF-β, PAI-1, AT) in Mexican Patients with Established Liver Fibrosis. Potential Correlation with Pirfenidone Treatment

2008; SAGE Publishing; Volume: 56; Issue: 7 Linguagem: Inglês

10.2310/jim.0b013e3181891512

1708-8267

Juan Armendáriz‐Borunda, Ana Rosa Rincón‐Sánchez, José Francisco Muñoz-Valle, Miriam Ruth Bueno‐Topete, Edith Oregón-Romero, María Cristina Islas-Carbajal, David Medina-Preciado, Ignacio Ferreira González, Carlos A Carmona Bautista, Sergio García-Rocha, Jesús María Godoy Bejarano, Mónica Vázquez-Del Mercado, Rogelio Troyo‐Sanromán, Inmaculada Arellano-Olivera, Silvia Lucano, Adriana Álvarez-Rodríguez, Adriana Salazar,

Chronic Myeloid Leukemia Treatments

The aim of this work was to establish a potential correlation between specific polymorphisms and presence of hepatic fibrosis in Mexican patients with established liver fibrosis (ELF). Second, necroinflammatory index improvement was correlated with Pirfenidone (PFD) treatment response and the same polymorphisms.We analyzed TGF-beta polymorphisms in codon 25, a single basepair guanine insertion-deletion polymorphism (4G/5G) for PAI-1 and angiotensin AT-6 single nucleotide polymorphism located in -6 promoter region. Twenty patients infected with either hepatitis C virus (HCV) (n = 13) or affected by alcohol consumption (n= 7) were included. Thirty subjects with no hepatic damage were included in control group. Blood samples for genomic DNA were obtained and plasminogen activator inhibitor-1 polymorphisms were done by polymerase chain reaction-artificial introduction of a restriction site, TGF-beta by polymerase chain reaction-amplification refractory mutation system and AT by polymerase chain reaction-restriction fragment length polymorphisms. Liver biopsies were obtained at baseline and after 12 months of PFD treatment.Established liver fibrosis patients had the homozygote G/G TGF-beta genotype, which has been associated with increased development of fibrosis. None of our patients had the G/C genotype. All pure HCV and pure alcohol abuse subjects carried G/G TGF-beta genotype (100% vs 37% control) (P = 0.0006). The odds of having TGF-beta G/G genotype was 19.5 for HCV patients and 10.83 for alcohol consumption patients as compared with healthy subjects (P < 0.001). Established liver fibrosis patients had an improvement in necroinflammatory index after PFD treatment when correlated with plasminogen activator inhibitor-1 and angiotensinogen-6 genotypes.Our data suggested that a combination of inherited polymorphisms increased the risk of advanced fibrosis in ELF patients. Pure HCV and pure alcohol consumption patients which were homozygous G/G carriers had 19.5- and 10.8-fold higher risk to develop advanced fibrosis respectively.