Association of genetic variation in the interferon gamma pathway with hepatitis B virus replication
Date Issued
2008
Date
2008
Author(s)
Huang, Hsuan-Hao
Abstract
Background: The role of host genetic factors in hepatitis B virus (HBV) replication activity remains largely unknown. We used both family-based association study and an independent set of unrelated subjects recruited from a longitudinal cohort study to investigate the association between single nucleotide polymorphisms (SNPs) in interferon gamma (IFNG) signaling pathway and circulating HBV DNA levels.aterials and Methods: Family-based study consisted of 729 HBV carriers from 269 families ascertained through a single HCC index patient. The longitudinal cohort study contained two groups: 1) 493 HBV carriers who had persistently high HBV DNA levels (defined as having a HBV DNA level≥ 4.39 log10 (copies/ml) for ≥4 years), and 2) 263 HBV carriers who had persistently low HBV DNA levels (defined as having a HBV DNA level< 4.39 log10 (copies/ml) for ≥4 years). A TaqMan assay was used to determine HBV DNA in plasma. We performed FBAT and QTDT for family-based association analysis, applied generalized linear mixed model to estimate the effect of at-risk genotypes on the change of plasma HBV DNA with time during up to 16 years of follow-up in unrelated subjects.esult: We found three significant SNPs in the IFNGR2 gene, with a false-discovery rate q value of <0.02. These associations were consistently observed in the family-based study and longitudinal study. In the STAT1 gene, four SNPs showed association with HBV DNA either in the family-based study or in the longitudinal study. The false-discovery rate q values for these associations range from 0.015 to 0.36. Further haplotype analysis discovered at-risk haplotypes in the STAT1 gene and IFNGR2 gene.onclusions: Both our family-based association study and longitudinal cohort study on unrelated individuals suggest that genetic variation in the IFNGR2 and STAT1 genes may play some role in the HBV replication activity. Further studies on re-sequencing the entire gene region or identification of the functions on SNPs are warranted.
Subjects
Hepatitis B virus
Family-based association study
Transmission disequilibrium test
Generalized linear mixed model
SDGs
Type
thesis
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