| Hepatitis B virus (HBV) infection is one of the major infectious diseases with more than 350 million chronic carriers worldwide, and persistent HBV infection has been considered as a multifactorial and polygenic disorder with viral, environmental and genetic components. It is important to study the association between the persistent HBV infection and the host genetic susceptibility. Single nucleotide polymorphism (SNP) is a powerful tool for identifying genetic susceptibilities to common complex diseases in recent years. An unknown number of other unidentified genes are likely to modify the susceptibility to persistent HBV infection. We have confirmed estrogen receptorα(ESR1) and CXCL10 have the association with the persistent HBV infection in Chinese by the population-based linkage disequilibrium / association study. However, the associated SNPs are located in non-coding region, it is necessary to identify the regulatory SNPs (rSNPs) based on the functional study.For SNPs in coding regions, it is often possible to predict consequences for protein structure and function, but most SNPs are found in non-coding DNA. These SNPs may affect gene regulation or they may have no biological consequence. Screening for SNPs that affect transcriptional regulation is commonly done by in vitro assays of electrophoretic mobility shift assay (EMSA) and plasmid reporter-gene expression. The biological relevance of these approaches is limited by the absence of a natural chromatin structure and regulation. Furthermore, SNPs are typically analyzed in isolation, whereas it may be the precise combination of SNPs on a given allele that determines regulatory significance. We therefore need ways of evaluating the effects of SNPs on transcriptional regulation in vivo, that is, in natural chromosomes in a normally functioning nucleus.This study aimed to find a sensitive method for detecting SNPs that affect gene regulation in vivo, even if there are no suitable genetic markers on the RNA transcript.
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