Possible involvement of cytokine gene polymorphisms in fulminant hepatitis.
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.
Takakura
Mihoko
M
Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Tokushige
Katsutoshi
K
Matsushita
Noriko
N
Hashimoto
Etsuko
E
Shiratori
Keiko
K
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*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10