Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients with chronic liver disease caused by HCV

Tokushige, Katsutoshi; Tsuchiya, Noriko; Hasegawa, Kiyoshi; Hashimoto, Etsuko; Yamauchi, Katsumi; Komatsu, Tatsuzi; Hayashi, Naoaki
January 2003
American Journal of Gastroenterology;Jan2003, Vol. 98 Issue 1, p160
Academic Journal
: ObjectiveTo 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.: MethodsWe 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).: ResultsThere 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-β 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.: ConclusionOur data suggest that TNF gene polymorphisms and HLA-DRB1 haplotype may influence the activity of HCV in chronic liver disease.


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