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- Publisher Website: 10.1002/hep.27608
- Scopus: eid_2-s2.0-84925352043
- PMID: 25418280
- WOS: WOS:000352099700021
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Article: The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B
Title | The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B |
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Authors | |
Issue Date | 2015 |
Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/ |
Citation | Hepatology, 2015, v. 61 n. 4, p. 1251-1260 How to Cite? |
Abstract | In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P=5.7 × 10-23, odds ratio=0.36) irrespective of hepatitis B virus surface antibody status (P=6.2 × 10-21 and 1.5 × 10-10, respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P=0.007). The estimated heritability explained by this single variation was ∼3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion: The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (Hepatology 2015;61:1251-1260). © 2014 by the American Association for the Study of Liver Diseases. |
Persistent Identifier | http://hdl.handle.net/10722/214309 |
ISSN | 2023 Impact Factor: 12.9 2023 SCImago Journal Rankings: 5.011 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Peng, L | - |
dc.contributor.author | Zhao, Q | - |
dc.contributor.author | Li, Q | - |
dc.contributor.author | Li, M | - |
dc.contributor.author | Li, C | - |
dc.contributor.author | Xu, T | - |
dc.contributor.author | Jing, X | - |
dc.contributor.author | Zhu, X | - |
dc.contributor.author | Wang, Y | - |
dc.contributor.author | Li, F | - |
dc.contributor.author | Sham, PC | - |
dc.contributor.author | Wang, J | - |
dc.date.accessioned | 2015-08-21T11:11:49Z | - |
dc.date.available | 2015-08-21T11:11:49Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Hepatology, 2015, v. 61 n. 4, p. 1251-1260 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10722/214309 | - |
dc.description.abstract | In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P=5.7 × 10-23, odds ratio=0.36) irrespective of hepatitis B virus surface antibody status (P=6.2 × 10-21 and 1.5 × 10-10, respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P=0.007). The estimated heritability explained by this single variation was ∼3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion: The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (Hepatology 2015;61:1251-1260). © 2014 by the American Association for the Study of Liver Diseases. | - |
dc.language | eng | - |
dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/ | - |
dc.relation.ispartof | Hepatology | - |
dc.rights | Hepatology. Copyright © John Wiley & Sons, Inc. | - |
dc.title | The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B | - |
dc.type | Article | - |
dc.identifier.email | Li, M: mxli@hku.hk | - |
dc.identifier.email | Sham, PC: pcsham@hkucc.hku.hk | - |
dc.identifier.authority | Li, M=rp01722 | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.identifier.doi | 10.1002/hep.27608 | - |
dc.identifier.pmid | 25418280 | - |
dc.identifier.scopus | eid_2-s2.0-84925352043 | - |
dc.identifier.hkuros | 246421 | - |
dc.identifier.volume | 61 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1251 | - |
dc.identifier.epage | 1260 | - |
dc.identifier.isi | WOS:000352099700021 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0270-9139 | - |