Sodium taurocholate cotransporting polypeptide (NTCP) was identified as an entry receptor for hepatitis B virus (HBV) infection. The substitution of serine at position 267 of NTCP with phenylalanine (S267F) is an Asian-specific variation that hampers HBV entry in vitro. In this study, we aimed to evaluate the prevalence of S267F polymorphism in Korean patients with chronic hepatitis B (CHB) and its association with disease progression and potential viral evolution in the preS1 domain of HBV. We found that the frequency of the S267F variant of NTCP in CHB patients and controls was 2.7% and 5.7% (P = 0.031), respectively, and that those who had S267F variant were less susceptible to chronic HBV infection. The frequency of the S267F variant in CHB, cirrhosis and hepatocellular carcinoma (HCC) patients was 3.3%, 0.9%, and 3.5%, respectively. Thus, the S267F variant correlated significantly with a lower risk for cirrhosis (P = 0.036). Sequencing preS1 domain of HBV from the patients who had S267F variant revealed no significant sequence change compared to the wild type. In conclusion, the S267F variant of NTCP is clinically associated with a lower risk of chronic HBV infection and cirrhosis development, which implicates suppressing HBV entry could reduce the disease burden.
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