TURNER NECROSIS FACTOR-ALPHA PROMOTER POLYMORPHISM AT POSITION-238 ISASSOCIATED WITH CHRONIC ACTIVE HEPATITIS-C INFECTION

Tumor necrosis factor alpha (TNF-alpha) is involved in the pathogenesi s of chronic hepatitis C virus infection. The gene for TNF-alpha is en coded in the major histocompatibility locus (MHC). Two polymorphisms a t positions -308 and -238 in the TNF-alpha promoter region might influ ence TNF-alpha expression. These promoter polymorphisms have been link ed previously to a number of infectious diseases. TNF-alpha promoter p olymorphisms at positions -238 and -308 were studied by DNA sequencing and sequence-specific oligonucleotide hybridization in 82 individuals with chronic hepatitis C and 99 control subjects. Subjects had been H LA class I and class Il typed in a previous study. The frequency of th e TNF238.2 promoter allele was significantly higher in the hepatitis C group (18.7%) compared to the controls (3.5%; P < 0.0001; pcorr < 0.0 09). No significant differences in the frequency of the TNF308.2 allel e were observed between patients and controls. The increased frequency of the TNF238.2 allele could not be explained by linkage disequilibri um to HLA-B or -DR genes. These findings show an association between t he TNF238.2 promoter variant and chronic active hepatitis C. They sugg est that this polymorphism or a linked gene may be a host factor contr ibuting to the development of chronic active hepatitis C. (C) 1998 Wil ey-Liss, Inc.