Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability
Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability
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NTCP p.Ser267Phe 变体对慢性 HBV 感染期间疾病进展和 HBV preS1 变异的多种影响
DOI：
10.3389/fcimb.2019.00018
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发表时间：
2019-03-01
影响因子：
5.7
通讯作者：
Peng, Liang
中科院分区：
文献类型：
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作者：
Yang, Fangji;Wu, Lina;Peng, Liang
牛磺胆酸钠共转运多肽 (NTCP) 作为宿主肝细胞上乙型肝炎病毒 (HBV) 感染的细胞受体。我们的目的是研究 NTCP p.Ser267Phe 变体如何影响 HBV 相关疾病的进展，并分析携带 p.Ser267Phe 变体的宿主遗传背景下的病毒基因组变异。共有 3187 名慢性乙型肝炎 (CHB) 患者入组并进行了 p.Ser267Phe 变体基因分型。通过逻辑回归分析评估该变异与疾病进展的关联。我们还招募了 83 名初治慢性乙型肝炎患者来分析 HBV preS1 区域的变异性。 NTCP p.Ser267Phe 变异的频率在诊断为慢加急性肝衰竭的患者中显着较低[OR (95% CI) = 0.33 (0.18–0.58), P = 1.34 × 10−4]，肝硬化[OR (95% CI) = 0.47 (0.31–0.72), P = 4.04 × 10−4]，调整后与加性模型下的 CHB 对照相比，肝细胞癌 [OR (95% CI) = 0.54 (0.34–0.86), P = 9.83 × 10−3]。此外，NTCP p.Ser267Phe 杂合子组中 HBV preS1 区域的氨基酸突变百分比显着高于 NTCP 野生型纯合子组（P < 0.05）。我们在此证明，NTCP p.Ser267Phe 变体是一种保护因子，可降低 CHB 患者发生肝衰竭、肝硬化和肝细胞癌的风险。携带 NTCP p.Ser267Phe 的宿主遗传背景会对病毒施加选择性压力，导致更多变异。
The sodium taurocholate co-transporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus (HBV) infection on host hepatocytes. We aim to investigate how the NTCP p.Ser267Phe variant affects HBV-related disease progression and analyze viral genomic variability under a host genetic background carrying the p.Ser267Phe variant. A total of 3187 chronic hepatitis B (CHB) patients were enrolled and genotyped for the p.Ser267Phe variant. The variant's association with disease progression was evaluated by logistic regression analysis. We also enrolled 83 treatment-naive CHB patients to analyze the variability of the HBV preS1 region. The frequency of the NTCP p.Ser267Phe variant was significantly lower in patients diagnosed with acute-on-chronic liver failure [OR (95% CI) = 0.33 (0.18–0.58), P = 1.34 × 10−4], cirrhosis [OR (95% CI) = 0.47 (0.31–0.72), P = 4.04 × 10−4], and hepatocellular carcinoma [OR (95% CI) = 0.54 (0.34–0.86), P = 9.83 × 10−3] as compared with CHB controls under the additive model after adjustment. Furthermore, the percentage of amino acid mutations in HBV preS1 region was significantly higher in the NTCP p.Ser267Phe heterozygote group than in the NTCP wild type homozygote group (P < 0.05). We herein demonstrate that the NTCP p.Ser267Phe variant is a protective factor reducing CHB patient risk for liver failure, cirrhosis, and hepatocellular carcinoma. A host genetic background carrying NTCP p.Ser267Phe exerts selective pressure on the virus, leading to more variability.