title: Fibrogenic polymorphisms (TGF-beta, PAI-1, AT) in Mexican patients with established liver fibrosis. Potential correlation with pirfenidone treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico. armendbo@cucs.udg.mx
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Rincón
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.forename: Miriam
authors.initials: M
authors.lastname: Bueno-Topete
authors.forename: Edith
authors.initials: E
authors.lastname: Oregón-Romero
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Islas-Carbajal
authors.forename: David
authors.initials: D
authors.lastname: Medina-Preciado
authors.forename: Ignacio
authors.initials: I
authors.lastname: González-García
authors.forename: C Alfredo
authors.initials: CA
authors.lastname: Bautista
authors.forename: Sergio
authors.initials: S
authors.lastname: García-Rocha
authors.forename: Jesús
authors.initials: J
authors.lastname: Godoy
authors.forename: Mónica
authors.initials: M
authors.lastname: Vázquez-Del Mercado
authors.forename: Rogelio
authors.initials: R
authors.lastname: Troyo-SanRoman
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Arellano-Olivera
authors.forename: Silvia
authors.initials: S
authors.lastname: Lucano
authors.forename: Adriana
authors.initials: A
authors.lastname: Alvarez-Rodríguez
authors.forename: Adriana
authors.initials: A
authors.lastname: Salazar
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008800:Mexico; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011728:Pyridones / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; D011728:Pyridones; C051321:SERPINE1 protein, human; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; C093844:pirfenidone