Chronic hepatitis B virus infection in Polynesians
Genetic differences between Polynesians and Europeans may contribute to the many differences in disease frequency that occur between these races. This thesis describes studies that were designed to determine if genetic influences contribute to the high prevalence of chronic hepatitis B virus (HBV) infection in Polynesians. Alleles suitable for gene flow measurements were identified and used to find associations between European genes and indices of chronic HBV infection in Polynesians. An ecologic study found a negative association between European genes and the prevalence of chronic HBV infection in five Polynesian ethnic groups (p<0.05). In a case control study, there was a positive correlation (r=0.90, p=0.04) between the percent of European genes in a Polynesian ethnic group and the difference in the percent of European genes between the HBV carriers and the anti-HBs positive controls in that ethnic group. Thus, the possibility that genetic factors are a major cause of the high prevalence of chronic HBV infection in Polynesians cannot be excluded. A twin study or candidate gene studies will be necessary to take this work further. We attempted to identify candidate genes in the Tcr ? chain variable region (V ?)locus that might contain polymorphisms that influence the human in vivo immune response to the HBV. V?7.4 was associated with the immune response to a vaccine containing recombinant HBsAg in two separate studies (p<0.0001 and p=0.05). The frequency of.V?7.4 was low in the cord blood of neonates born to HBsAg positive mothers (p=0.001). The frequency of V?5.1 was high in the cord blood of neonates of HBeAg positive mothers (p<0.001). Thus the V?7.4 and V?5.1 genes may be preferentially used in the human immune response to the HBV and may be an appropriate place to seek polymorphisms that influence the immune response to the HBV and susceptibility to a chronic HBV infection.