T. Hohler et al., A TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) PROMOTER POLYMORPHISM IS ASSOCIATED WITH CHRONIC HEPATITIS-B INFECTION, Clinical and experimental immunology, 111(3), 1998, pp. 579-582
Cytokines such as TNF-alpha and interferon gamma (IFN-gamma) are impor
tant for the elimination of infected hepatocytes during acute hepatiti
s B virus (HBV) infection. Two G versus A transitions in the TNF-alpha
promoter region at positions -308 and -238 possibly influence TNF-alp
ha expression. We investigated these TNF-alpha polymorphisms in 71 pat
ients with chronic HBV infection, in 32 subjects that had spontaneousl
y recovered from acute HBV infection, and in 99 healthy controls. The
-238 A promoter variant was present in 18 (25%) of 71 patients with ch
ronic HBV infection compared with two (6%) of 32 subjects with acute i
nfection (P<0.04), and seven (7%) of 99 controls (P<0.003). By contras
t, the prevalence of the variant at position -308 was similar in all i
nvestigated groups. The observed differences could not be explained by
linkage disequilibrium to HLA-B or -DRB1 alleles. These findings sug
gest an association between the TNF-alpha promoter polymorphism at pos
ition -238 and the development of chronic HBV infection. This promoter
variant appears to be linked to defective viral clearance.