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Article: Rare inborn errors associated with chronic hepatitis B virus infection

TitleRare inborn errors associated with chronic hepatitis B virus infection
Authors
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2012, v. 56 n. 5, p. 1661-1670 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/164368
ISSN
2014 Impact Factor: 11.055
2014 SCImago Journal Rankings: 4.310
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhao, Qen_HK
dc.contributor.authorPeng, Len_HK
dc.contributor.authorHuang, Wen_HK
dc.contributor.authorLi, Qen_HK
dc.contributor.authorPei, Yen_HK
dc.contributor.authorYuan, Pen_HK
dc.contributor.authorZheng, Len_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorDeng, Jen_HK
dc.contributor.authorZhong, Cen_HK
dc.contributor.authorHu, Ben_HK
dc.contributor.authorDing, Hen_HK
dc.contributor.authorFang, Wen_HK
dc.contributor.authorLi, Ren_HK
dc.contributor.authorLiao, Qen_HK
dc.contributor.authorLin, Cen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorYan, Hen_HK
dc.contributor.authorHou, Jen_HK
dc.contributor.authorWu, Qen_HK
dc.contributor.authorXu, Ten_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorPeng, Ten_HK
dc.contributor.authorChen, Sen_HK
dc.contributor.authorLai, KNen_HK
dc.contributor.authorYuen, MFen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorMaini, MKen_HK
dc.contributor.authorLi, Cen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorGao, ZLen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2012-09-20T07:58:19Z-
dc.date.available2012-09-20T07:58:19Z-
dc.date.issued2012en_HK
dc.identifier.citationHepatology, 2012, v. 56 n. 5, p. 1661-1670en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/164368-
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.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.titleRare inborn errors associated with chronic hepatitis B virus infectionen_HK
dc.typeArticleen_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.emailYuen, MF: mfyuen@hku.hken_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/hep.25850en_HK
dc.identifier.pmid22610944-
dc.identifier.scopuseid_2-s2.0-84868193316en_HK
dc.identifier.hkuros210615en_US
dc.identifier.hkuros226193-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84868193316&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume56en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1661en_HK
dc.identifier.epage1670en_HK
dc.identifier.isiWOS:000310543100011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhao, Q=55387783900en_HK
dc.identifier.scopusauthoridPeng, L=7201574287en_HK
dc.identifier.scopusauthoridHuang, W=55387852000en_HK
dc.identifier.scopusauthoridLi, Q=55386984400en_HK
dc.identifier.scopusauthoridPei, Y=36020211700en_HK
dc.identifier.scopusauthoridYuan, P=46761647300en_HK
dc.identifier.scopusauthoridZheng, L=55387067600en_HK
dc.identifier.scopusauthoridZhang, Y=50562456900en_HK
dc.identifier.scopusauthoridDeng, J=55387298600en_HK
dc.identifier.scopusauthoridZhong, C=55386983900en_HK
dc.identifier.scopusauthoridHu, B=36087575900en_HK
dc.identifier.scopusauthoridDing, H=49961258500en_HK
dc.identifier.scopusauthoridFang, W=55387549400en_HK
dc.identifier.scopusauthoridLi, R=35205366000en_HK
dc.identifier.scopusauthoridLiao, Q=55387469100en_HK
dc.identifier.scopusauthoridLin, C=23498205800en_HK
dc.identifier.scopusauthoridDeng, W=55387544100en_HK
dc.identifier.scopusauthoridYan, H=54898685200en_HK
dc.identifier.scopusauthoridHou, J=7401966118en_HK
dc.identifier.scopusauthoridWu, Q=9133950800en_HK
dc.identifier.scopusauthoridXu, T=53464505700en_HK
dc.identifier.scopusauthoridLiu, J=55387907100en_HK
dc.identifier.scopusauthoridHu, L=55205386300en_HK
dc.identifier.scopusauthoridPeng, T=36103428000en_HK
dc.identifier.scopusauthoridChen, S=55387117100en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK
dc.identifier.scopusauthoridWang, Y=55387157100en_HK
dc.identifier.scopusauthoridMaini, MK=7003333032en_HK
dc.identifier.scopusauthoridLi, C=55387535700en_HK
dc.identifier.scopusauthoridLi, M=55387778800en_HK
dc.identifier.scopusauthoridWang, J=55387915000en_HK
dc.identifier.scopusauthoridZhang, X=55387493400en_HK
dc.identifier.scopusauthoridSham, PC=55387268100en_HK
dc.identifier.scopusauthoridWang, J=36984389800en_HK
dc.identifier.scopusauthoridGao, ZL=7402832732en_HK
dc.identifier.scopusauthoridWang, Y=13310049900en_HK

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