Genetic mimicry by hepatitis B virus.

Abstract

THE genetic hypothesis concerning the distribution of hepatitis B antigen (HBsAg, Australia antigen) carriers was proposed by Blumberg1 and states that susceptibility to the chronic asymptomatic carrier state is determined by a simple autosomal recessive gene (Au1). Persons homozygous for this gene (Au1/Au1) should become chronic carriers of the virus when infected with hepatitis B virus (HBV), whereas those heterozygous (Au1/Au0) or negative for the susceptibility gene (Au0/Au0) should not. Asymptomatic carriers of HBsAg are presumably chronically infected with HBV. Although independent segregation analyses of HBsAg in the families of blood donors2,3 and natural populations1,4–6 have failed to reject this hypothesis, it cannot account for the occurrence of a set of identical twins in which one twin had antigen, whereas the other had antibody2; nor for children with anti-HBs or without antigen in families where both parents were carriers of HBsAg (refs 3, 6 and 7). Indirect support for genetic control of the outcome of HBV infection comes from studies of thalassaemic patients in Italy8 and asymptomatic carriers in the Solomon Islands9. These have suggested that susceptibility to the chronic HBsAg carrier state may be linked to heterozygosity of Gm genes and the resulting inability to synthesise as many kinds of anti-Gm. This hypothesis has not been supported, however, by subsequent investigations of other populations10,11. On the basis of results presented here of segregation analysis carried out on data from the Solomon Islands, we have been able to reject the existence of a susceptibility gene as a major factor leading to the HBsAg carrier state in this population.