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Article: The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B

TitleThe p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B
Authors
Issue Date2015
PublisherJohn 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?
AbstractIn 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 Identifierhttp://hdl.handle.net/10722/214309
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPeng, L-
dc.contributor.authorZhao, Q-
dc.contributor.authorLi, Q-
dc.contributor.authorLi, M-
dc.contributor.authorLi, C-
dc.contributor.authorXu, T-
dc.contributor.authorJing, X-
dc.contributor.authorZhu, X-
dc.contributor.authorWang, Y-
dc.contributor.authorLi, F-
dc.contributor.authorSham, PC-
dc.contributor.authorWang, J-
dc.date.accessioned2015-08-21T11:11:49Z-
dc.date.available2015-08-21T11:11:49Z-
dc.date.issued2015-
dc.identifier.citationHepatology, 2015, v. 61 n. 4, p. 1251-1260-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10722/214309-
dc.description.abstractIn 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.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatology-
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.titleThe p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B-
dc.typeArticle-
dc.identifier.emailLi, M: mxli@hku.hk-
dc.identifier.emailSham, PC: pcsham@hkucc.hku.hk-
dc.identifier.authorityLi, M=rp01722-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.doi10.1002/hep.27608-
dc.identifier.pmid25418280-
dc.identifier.scopuseid_2-s2.0-84925352043-
dc.identifier.hkuros246421-
dc.identifier.volume61-
dc.identifier.issue4-
dc.identifier.spage1251-
dc.identifier.epage1260-
dc.identifier.isiWOS:000352099700021-
dc.publisher.placeUnited States-

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