| Hepatitis B severely threatens to the health of the people. The outcome of hepatitis B virus (HBV) infection is highly variable, ranging from asymptomatic diseases culminating in the spontaneous elimination of infection to persistent infection that can lead to cirrhosis, liver failure or hepatocellular carcinoma (HCC). The factors which determine the outcome in an individual patient are poorly understood but may be classified into three categories: viral, host and environmental factors.The broad definition of HBV variation includes genotype which embodys the difference of HBV among the people and viral mutation in an individual patients. The accumulation of the various mutants leads to the viral heterogeneity within the infected individuality, which called quasispecies. HBV possesses quassispecies characteristic may be a very important virological factor that brings about chronic hepatitis B and failure in antiviral treatment. Host genetic factors play an important role to determine the susceptibility to HBV and the outcome of HBV infection. The progress of human genome research by positional cloning and whole genome linkage analysis brings an optimistical prospect for mapping and identification of gene polymorphism which is associated with susceptibility or resistance to diseases. Major objects include twins, sibling pairs, adoptee, family pedigrees and epidemiological study. Twins study, an ideal research model has been used widely to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations. Clinical data shows infectious rate of HBV through mother to baby transmisson is higher for twins than sibling pairs. Thus the perfect phenomenon come into being that the two people who share a common set of genes are infected simultaneously by the same virus. They will have the identical outcome which usually obey the rule of reaction-time genetics. So the matching study of monozygotic (MZ) twins and dizygotic (DZ) twins for the same or different viral infection respectively may be useful to reveal the importance of host genetic factors to determine outcome of HBV infection with the multivariate analysis of the influence factors: inheritance, immune response, HBVvariation, enviroment and clinical manifestation.In this paper, the twins and sibling pairs infected with HBV as objectives, we preliminary investigated the relationship between the quasispecies of preS1/S2 region of HBV and the clinical manifestation of twins and siblings. Zygosity of twins was diagnosed by microsatellite polymorphism. To identify the serological model and exclude the evidence of coinfection with other virus, we detected HAV～HEV serological markers by ELISA method. HBV DNA level was detected by Lightcycler Fluorescent Quantitative system and Liver function (ALT, AST, TBil) was detected by HITACHI7250 Biochemistry detection system. We want to clarify the role of host factors to affect the clinical phenotype of hepatitis B through comparatively analyzing the model of serological markers, infectious rate, concordance rate, diseases phenotype concordance rate, the patterns of serological markers among the twins and siblings. We obtained 6 patients with high HBV DNA level and were divided into 3 groups. The experimental procedure was LPCR (amplification of 3.2kb genome DNA of HBV) -TA cloning-quasispecies detection-nucleotide sequence analysis.The major research results are as follows:1. Among 20 pairs of twins infected with HBV or with high risk to infection, the zygosity of 14 pairs of MZ twins and 6 pairs of DZ twins were identified by Genescan with 28 STR markers, the probability that any twins pair were MZ if all markers were concordant was 99.99999999%. 2. The genotype B and C of HBV were found in these 6 patients. Specifically, one pair of MZ twins were infected by HBV genotype B and C respectively which indicated the source of pathogen was different, one pair of DZ twins were infected by HBV genotype B and one sibling pair were infected by HBV genotype C.
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