title: A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers.
abstract: OBJECTIVE
  Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV-infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported.
  
  
  METHODS
  Three hundred and thirty-seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty-four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models.
  
  
  RESULTS
  Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014-0.349, P = 0.001).
  
  
  CONCLUSIONS
  The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.
authors.affiliation: Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juarez
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Celia
authors.initials: C
authors.lastname: Cifuentes
authors.forename: José A
authors.initials: JA
authors.lastname: Mira
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D002353:Carrier State / Q000821:virology*; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics / Q000821:virology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics*; D016015:Logistic Models; D009124:Muscle Proteins / Q000235:genetics; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009124:Muscle Proteins; D011092:Polyethylene Glycols; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D012254:Ribavirin; D018631:ras Proteins; C430100:BCL2L12 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494232:IRF3 protein, human; C085929:RRAS protein, human; C100416:peginterferon alfa-2a
keywords: BCL2L12; IL28B; IRF3; RRAS; SCAF1; SNPs; cirrhosis; genetics; hepatitis C virus; polymorphism