碩士 / 國立臺灣大學 / 流行病學研究所 / 87 / Background: While the hepatitis B virus (HBV) mass vaccination program has achieved an initial success, a small fraction of vaccine failure still occurs. In order to investigate whether the genetic determinants for vaccine failure (i.e. vaccine unresponsivenes and HBV persistent infection) exist, we conducted a family casecontrol study and a population based serosurvey to explore the importance of genetic basis.
Subjects: In the family case-control study, 261 family members of the 106 proband children (belong to carriers, noncarriers, and lower responders or higher responders to HBV vaccination), including multiple ethnic groups of Han and several indigenous minorities in Taiwan, were recrujited. In the population based study, 357 fully vaccinated Pulong children, aged 3-6 years old, were recruited from the serosurvey of Nanto Indigenous Village.
Methods: All HBV serological markers were examined by enzyme linked immunosorbant assay (ELISA) and some by radioimmunoassay (RIA). HBV DNA from plasma was detected by polymerase chain reaction (PCR). HLA class I (-A,-B), HLA class II (-DRB1), and polymorphism of TNF-□ promoter (-238,-308) were genotyped by sequence-specific oligonucleotide probe hybridization method (PCR-SSOP) and some verified by DNA sequence analysis.
Results: In the population based study, anti-HBs titers among HBsAg seronegative Pulong children were lower than that of Han childern (Mantel- Haenszel test for trend, P=0.02). The frequency of HLA-A02 allele was noted to be positively correlated with a higher anti-HBs antibody level in the Pulong minority children, yet no specific A02 alleles were prevail. In the family casecontrol study, the potential shared genetic susceptibility of family members was studied by genotyping HLA for each proband child and their family members. The frequency of HLA-A02 allele was found to be higher among vaccinated children with a higher level of anti-HBs (Chi-sqaure test, P=0.00024; Corrected Pc=0.0012) and further substantiated in the TDT analysis. In addition, the frequency of HLA-DRB1*14 was significantly higher in carrier children (50%) but underrepresented in the high anti-HBs responder group (0%). This result was also supported by the examination with the transmission disequilibrium test (TDT) among child/parents pairs (McNemar's test, P=0.01; P=0.04). When analyzed the HBV genotype in the carrier probands, a significantly association between HLA-A02 allele and HBV 'a' determinant variants was found (Fisher exact method, P=0.012).
Conclusion: We concluded that genetic predisposition to vaccine response and chronic HBV infection exits. HLA-A2 is associated with antibody response to HBV vaccination and is associated with the occurrence of immune escape HBV variants. Via what mechanism that HLA-A2 might link to B cell response remains to be elucidated. Furthermore, this is the first study to identify the correlation between HLA-DRB1*14 and chronic HBV infection in addition to HBV vaccine unresponsiveness. Understanding the genetic basis for HBV vaccine response and HBV chronic infection could provide potential means to improve HBV infection control in targeted infection.
| Identifer | oai:union.ndltd.org:TW/087NTU03544001 |
| Date | January 1999 |
| Creators | 仇琍茵 |
| Contributors | 何美鄉 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | en_US |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 89 |
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