title: Possible involvement of cytokine gene polymorphisms in fulminant hepatitis.
abstract: OBJECTIVE
  Host genetic factors have been reported as influencing the progress to fulminant hepatitis (FH). Our previous data showed the serum level of tumor necrosis factor (TNF)-alpha influenced by gene polymorphisms to be markedly increased. It was investigated whether polymorphisms in the IL-10 gene, in addition to TNF-alpha and -beta gene polymorphisms, might contribute to the pathogenesis of FH.
  
  
  METHODS
  We analyzed 42 patients with FH, 78 patients with acute hepatitis (AH), and 149 healthy subjects (control). IL-10 polymorphism sites at promoter regions -1028, -819, -592; TNF-alpha polymorphism sites at promoter regions -1031, -863, -857, -308, -238; and TNF-beta first intron Nco1 sites were studied. IL-10 gene polymorphisms were classified into three groups: low IL-10-producing haplotypes (ATA/ATA), intermediate haplotypes (ATA or CCA/CCA), and high haplotypes (ATA/ATG or CCG).
  
  
  RESULTS
  The allelic frequency of B2 in the TNF-beta gene was significantly higher in FH patients compared with the control group. The three groups showed no differences in polymorphisms of positions -1031, -863, -857, -308 and -238 in the TNF-alpha gene. The frequency of low IL-10-producing haplotypes tended to be higher in FH patients compared with control and that of high IL-10-producing haplotype tended to be lower in FH patients compared with control. The carrier rate with both the IL-10 haplotype and the TNF-beta gene B2/B2 was significantly higher than control.
  
  
  CONCLUSIONS
  Variations of cytokine polymorphisms including IL-10 and TNF-beta genes may be attributable to the pathogenesis of FH.
authors.affiliation: Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Takakura
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Tokushige
authors.forename: Noriko
authors.initials: N
authors.lastname: Matsushita
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hashimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiratori
mesh_terms: D000208:Acute Disease; D000328:Adult; D005260:Female; D006525:Hepatitis, Viral, Human / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D017114:Liver Failure, Acute / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10