Several studies have reported that the genotype

Several studies have reported that the genotype and allele frequencies of S267F vary considerably between different study groups and geographical regions (Ezzikouri et al., 2017, Hu et al., 2016, Lee et al., 2017, Li et al., 2014, Pan et al., 2011, Peng et al., 2015, Yang et al., 2016, Zhang et al., 2017). Here, we report that the frequencies of the genotypes CC, CT and TT are 83.6%, 15.9% and 0,5%, respectively, among 214 Vietnamese healthy individuals. The frequency of the S267F genotypes CT and TT in our study was lower than in other Asian populations, e.g. in the Chinese Han (20.4%) and Taiwanese (18.5%) (Hu et al., 2016, Peng et al., 2015), but more common than in the Korean population (5.7%) (Lee et al., 2017). Although the occurrence of S267F was significantly lower in HBV patients than in HCs in most studies, including our present study, its frequency is regionally different, ranging from 0.9% to 18% (Ezzikouri et al., 2017, Hu et al., 2016, Lee et al., 2017, Li et al., 2014, Pan et al., 2011, Peng et al., 2015, Yang et al., 2016, Zhang et al., 2017). A protective effect of S267F in HBV infection has been reported in previous studies, indicating that individuals with the S267F variant were 2–5-fold less susceptible to chronic HBV infection (Hu et al., 2016, Lee et al., 2017, Peng et al., 2015). Our study yields corresponding results (OR=0.3, 95% CI=0.19–0.54). The protective effect of S267F on HBV infection has also been demonstrated in in vitro experiments, showing that in mixed acpt mg of wild-type NTCP and S267F at a 1:1 ratio the efficiency of HBV infection was higher than 70% (Yan et al., 2014), suggesting that the T allele of S267F contributes to a certain degree to resist HBV infection. Similarly, we observed that the T allele of S267F contributes to reducing the risk of CHB (OR=0.34). The earlier studies have also shown that S267F is independently associated with a decreased risk of progression to LC and/or HCC (Hu et al., 2016, Lee et al., 2017, Wang et al., 2017). In our study, when comparing HBV patients with advanced stages of LC and HCC with HCs, those carrying S267F had a significantly decreased risk of developing LC or HCC, indicating a lower probability of unfavorable clinical outcome compared to individuals carrying the wild-type genotype. The substitution of serine, a hydrophilic residue, by phenylalanine, a large hydrophobic residue, alters the structure of NTCP and causes a modification of the HBV/HDV receptor function (Yan et al., 2012), but also results in a reduced function of bile acid transport (Ho et al., 2004). Bile acids are cytotoxic compounds, and as their concentrations increase in the liver, they trigger hepatocyte apoptosis by activating the death receptor interactive signaling pathway, thereby promoting persistent inflammatory injury (Faubion et al., 1999, Ho et al., 2004, Miyoshi et al., 1999). The NTCP S267F variant decreases uptake of bile acids into hepatocytes, thus reducing accumulation of intrahepatic cytotoxic bile salts (Ho et al., 2004). Decreased uptake of bile acids into hepatocytes is associated with mild hypotonia, growth retardation, and delayed motor milestones (Vaz et al., 2015). However, the relationship between reduced bile salt uptake into hepatocytes and lower risk of LC and HCC development warrants further investigation.
Acknowledgements
Introduction microRNAs (miRNAs) are endogenous, small noncoding RNAs with length of 21–25 nucleotides. miRNAs control gene expression by degrading or suppressing the translation of target mRNAs [1]. miRNAs have been demonstrated to be involved in many biological and pathological processes including virus infection [[2], [3], [4], [5]]. Recent data indicated that virus infection caused the change of host miRNAs expression profile, which may affect virus replication and virus-associated diseases [5]. Therefore, the study on the role of miRNAs in host-virus interactions will be of great importance for understanding the pathogenesis and biology of viruses.