Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients with chronic liver disease caused by HCV.
OBJECTIVE
To clarify the host genomic role in chronic liver disease associated with hepatitis C virus (HCV), we investigated the relationship between the severity of hepatitis and the polymorphisms of the tumor necrosis factor (TNF) gene or the human leukocyte antigen (HLA)-DRB1 haplotypes.


METHODS
We analyzed 40 healthy subjects, 50 patients with chronic inactive hepatitis caused by HCV with mean serum ALT concentrations under 40 IU/ml (group A), and 50 patients with chronic active liver disease caused by HCV and mean ALT concentrations over 50 IU/ml (group B).


RESULTS
There were no significant differences in the frequencies of TNF promoter gene variants at positions -238 and -308 between the groups. Regarding polymorphisms at the TNF-beta NcoI site, the frequency of B1B1 homozygotes in group A was significantly increased, compared with the healthy subjects and those in group B (controls 7.5%, group A 34%, group B 10%). Regarding the analysis of HLA-DRB1, DRB1*0901 was significantly more frequent in group A than in group B (group A 19%, group B 5%). TNF B1B1 homozygotes were associated with HLA-DRB1*0901 and *1302, and negatively associated with DRB1*0405. Combination analysis revealed that HCV was inactive in the majority of patients who were both DRB1*0901 and B1B1 homozygotes.


CONCLUSIONS
Our data suggest that TNF gene polymorphisms and HLA-DRB1 haplotype may influence the activity of HCV in chronic liver disease.
Tokushige
Katsutoshi
K
Division of Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
Tsuchiya
Noriko
N
Hasegawa
Kiyoshi
K
Hashimoto
Etsuko
E
Yamauchi
Katsumi
K
Komatsu
Tatsuzi
T
Hayashi
Naoaki
N
D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha