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Article: Rare inborn errors associated with chronic hepatitis B virus infection
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TitleRare inborn errors associated with chronic hepatitis B virus infection
 
AuthorsZhao, Q10
Peng, L10
Huang, W10
Li, Q6
Pei, Y2 10
Yuan, P10
Zheng, L10
Zhang, Y10
Deng, J10
Zhong, C10
Hu, B10
Ding, H10 7
Fang, W9 10
Li, R12
Liao, Q6
Lin, C10
Deng, W4
Yan, H10
Hou, J10
Wu, Q10
Xu, T11
Liu, J11
Hu, L11
Peng, T11
Chen, S10
Lai, KN5
Yuen, MF5
Wang, Y8
Maini, MK1
Li, C10
Li, M5
Wang, J6
Zhang, X6
Sham, PC5
Wang, J6 3
Gao, ZL10
Wang, Y10
 
Issue Date2012
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
CitationHepatology, 2012, v. 56 n. 5, p. 1661-1670 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.25850
 
AbstractChronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10 -7, 2.76 × 10 -5, 5.08 × 10 -5, 2.78 × 10 -4 and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10 -16. As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). Conclusion: We identified four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute to increased host susceptibility to CHB. © 2012 American Association for the Study of Liver Diseases.
 
ISSN0270-9139
2013 Impact Factor: 11.190
 
DOIhttp://dx.doi.org/10.1002/hep.25850
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhao, Q
 
dc.contributor.authorPeng, L
 
dc.contributor.authorHuang, W
 
dc.contributor.authorLi, Q
 
dc.contributor.authorPei, Y
 
dc.contributor.authorYuan, P
 
dc.contributor.authorZheng, L
 
dc.contributor.authorZhang, Y
 
dc.contributor.authorDeng, J
 
dc.contributor.authorZhong, C
 
dc.contributor.authorHu, B
 
dc.contributor.authorDing, H
 
dc.contributor.authorFang, W
 
dc.contributor.authorLi, R
 
dc.contributor.authorLiao, Q
 
dc.contributor.authorLin, C
 
dc.contributor.authorDeng, W
 
dc.contributor.authorYan, H
 
dc.contributor.authorHou, J
 
dc.contributor.authorWu, Q
 
dc.contributor.authorXu, T
 
dc.contributor.authorLiu, J
 
dc.contributor.authorHu, L
 
dc.contributor.authorPeng, T
 
dc.contributor.authorChen, S
 
dc.contributor.authorLai, KN
 
dc.contributor.authorYuen, MF
 
dc.contributor.authorWang, Y
 
dc.contributor.authorMaini, MK
 
dc.contributor.authorLi, C
 
dc.contributor.authorLi, M
 
dc.contributor.authorWang, J
 
dc.contributor.authorZhang, X
 
dc.contributor.authorSham, PC
 
dc.contributor.authorWang, J
 
dc.contributor.authorGao, ZL
 
dc.contributor.authorWang, Y
 
dc.date.accessioned2012-09-20T07:58:19Z
 
dc.date.available2012-09-20T07:58:19Z
 
dc.date.issued2012
 
dc.description.abstractChronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10 -7, 2.76 × 10 -5, 5.08 × 10 -5, 2.78 × 10 -4 and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10 -16. As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). Conclusion: We identified four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute to increased host susceptibility to CHB. © 2012 American Association for the Study of Liver Diseases.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationHepatology, 2012, v. 56 n. 5, p. 1661-1670 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.25850
 
dc.identifier.doihttp://dx.doi.org/10.1002/hep.25850
 
dc.identifier.epage1670
 
dc.identifier.hkuros210615
 
dc.identifier.hkuros226193
 
dc.identifier.issn0270-9139
2013 Impact Factor: 11.190
 
dc.identifier.issue5
 
dc.identifier.pmid22610944
 
dc.identifier.scopuseid_2-s2.0-84868193316
 
dc.identifier.spage1661
 
dc.identifier.urihttp://hdl.handle.net/10722/164368
 
dc.identifier.volume56
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofHepatology
 
dc.relation.referencesReferences in Scopus
 
dc.titleRare inborn errors associated with chronic hepatitis B virus infection
 
dc.typeArticle
 
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<description.abstract>Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of &lt;1.0 &#215; 10 -7, 2.76 &#215; 10 -5, 5.08 &#215; 10 -5, 2.78 &#215; 10 -4 and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was &lt;2.0 &#215; 10 -16. As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). Conclusion: We identified four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute to increased host susceptibility to CHB. &#169; 2012 American Association for the Study of Liver Diseases.</description.abstract>
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Author Affiliations
  1. UCL
  2. Longgang district of Shenzhen Women and Children Hospital
  3. Københavns Universitet
  4. Guangdong Provincial Hospital of Traditional Chinese Medicine
  5. The University of Hong Kong
  6. BGI-Shenzhen
  7. Guangdong Women and Children Hospital
  8. Chinese Center for Disease Control and Prevention
  9. Shaanxi Provincial People's Hospital
  10. Sun Yat-Sen University
  11. Chinese Academy of Sciences
  12. Guangzhou Medical College