Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Department of Biotechnology, Yonsei University, Seoul, Korea.
Sci Rep. 2017 Dec 15;7(1):17634. doi: 10.1038/s41598-017-17959-x.
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.
牛磺胆酸钠共转运蛋白 (NTCP) 被鉴定为乙型肝炎病毒 (HBV) 感染的进入受体。NTCP 位置 267 处丝氨酸被苯丙氨酸取代 (S267F) 是一种亚洲特异性变异，可阻碍 HBV 在体外进入。在这项研究中，我们旨在评估 S267F 多态性在韩国慢性乙型肝炎 (CHB) 患者中的流行率及其与疾病进展的关系，并评估其在 HBV 前 S1 区潜在的病毒进化。我们发现 CHB 患者和对照组中 NTCP 的 S267F 变体的频率分别为 2.7%和 5.7%（P = 0.031），并且具有 S267F 变体的患者对慢性 HBV 感染的易感性较低。在 CHB、肝硬化和肝细胞癌 (HCC) 患者中，S267F 变体的频率分别为 3.3%、0.9%和 3.5%。因此，S267F 变体与肝硬化的风险降低显著相关（P = 0.036）。与野生型相比，来自具有 S267F 变体的患者的 HBV 前 S1 区序列没有发现显著的序列变化。总之，NTCP 的 S267F 变体与慢性 HBV 感染和肝硬化发展的风险降低相关，这表明抑制 HBV 进入可能会降低疾病负担。
