title: Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients.
abstract: Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP) at position -238 and -308 of the tumor necrosis factor alpha (TNF-α) and -592 of the interleukin-10 (IL-10) promotor genes) and of classical factors (age, alcohol, immunodepression, antirretroviral therapy) on the risk of liver cirrhosis in human immunodeficiency (HIV)-hepatitis C (HCV) virus coinfected patients.
  
  
  
  Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis) and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load) and HCV-related (serum ALT concentration, HCV viral load, HCV genotype) characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α) and -592 of the interleukin-10 (IL-10) promotor genes were studied.
  
  
  
  Evolution time of the infection was 21 years in both patients' groups (chronic hepatitis and liver cirrhosis). The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection), a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis.
  
  
  
  It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position), above other factors previously accepted (age, gender, alcohol, immunodepression), on the evolution to liver cirrhosis among HIV-infected patients with established chronic HCV infections.
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Corchado
authors.forename: Mercedes
authors.initials: M
authors.lastname: Márquez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Montes de Oca
authors.forename: Paula
authors.initials: P
authors.lastname: Romero-Cores
authors.forename: Clotilde
authors.initials: C
authors.lastname: Fernández-Gutiérrez
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Girón-González
mesh_terms: D000328:Adult; D000368:Aged; D060085:Coinfection / Q000235:genetics / Q000276:immunology; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10