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Article: A non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infection

TitleA non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infection
Authors
KeywordsHBV infection
IFNAR1
Protein stability
SNP
Issue Date2009
PublisherBlackwell Publishing Ltd
Citation
Journal Of Viral Hepatitis, 2009, v. 16 n. 1, p. 45-52 How to Cite?
AbstractThe type I interferon (IFN-α/β) receptor 1 (IFNAR1) mediates the potent antiviral and immuno-regulatory effects of IFN-α/β that are believed to be pivotal to eradicate hepatitis B virus (HBV) infection. IFNAR1 promoter polymorphisms (at -568/-77) have been shown to be associated with susceptibility to chronic HBV infection; however, whether these markers are genetic determinants of HBV infection remains unknown. The functional significance of promoter -568/-77 polymorphisms was assessed by mutagenesis and luciferase assays. Sequencing and restriction fragment length polymorphisms in 328 chronic HBV patients, 130 spontaneous resolvers and 148 healthy blood donors identified other polymorphism at IFNAR1 open reading frame. IFNAR1 expression levels in peripheral blood cells were detected by flow cytometry. We found that the -568/-77 promoter variants were unlikely to affect transcription levels. A C/G single nucleotide polymorphism, in strong linkage disequilibrium with the promoter polymorphisms, was found in the coding sequence of IFNAR1 (nt19158). This resulted in a nonsynonymous substitution in the extracellular region of IFNAR1 protein and correlated with susceptibility to chronic HBV infection. Bioinformatic analysis suggested decreased stability of the IFNAR1 protein. Chronic HBV patients with the 19158C/C genotype (Leu141) exhibited higher IFNAR1 protein expression levels in peripheral blood monocytes than those with the 19158G/G genotype (Val141). In conclusion, IFNAR1 19158C/G polymorphism is primarily associated with susceptibility to chronic HBV infection. © 2008 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/58294
ISSN
2015 Impact Factor: 4.179
2015 SCImago Journal Rankings: 1.815
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

This work was supported in part by the University Development Fund of the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorZhou, Jen_HK
dc.contributor.authorSmith, DKen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorPoon, VKMen_HK
dc.contributor.authorNg, Fen_HK
dc.contributor.authorChen, DQen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorCao, KYen_HK
dc.contributor.authorZheng, BJen_HK
dc.date.accessioned2010-05-31T03:27:36Z-
dc.date.available2010-05-31T03:27:36Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Viral Hepatitis, 2009, v. 16 n. 1, p. 45-52en_HK
dc.identifier.issn1352-0504en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58294-
dc.description.abstractThe type I interferon (IFN-α/β) receptor 1 (IFNAR1) mediates the potent antiviral and immuno-regulatory effects of IFN-α/β that are believed to be pivotal to eradicate hepatitis B virus (HBV) infection. IFNAR1 promoter polymorphisms (at -568/-77) have been shown to be associated with susceptibility to chronic HBV infection; however, whether these markers are genetic determinants of HBV infection remains unknown. The functional significance of promoter -568/-77 polymorphisms was assessed by mutagenesis and luciferase assays. Sequencing and restriction fragment length polymorphisms in 328 chronic HBV patients, 130 spontaneous resolvers and 148 healthy blood donors identified other polymorphism at IFNAR1 open reading frame. IFNAR1 expression levels in peripheral blood cells were detected by flow cytometry. We found that the -568/-77 promoter variants were unlikely to affect transcription levels. A C/G single nucleotide polymorphism, in strong linkage disequilibrium with the promoter polymorphisms, was found in the coding sequence of IFNAR1 (nt19158). This resulted in a nonsynonymous substitution in the extracellular region of IFNAR1 protein and correlated with susceptibility to chronic HBV infection. Bioinformatic analysis suggested decreased stability of the IFNAR1 protein. Chronic HBV patients with the 19158C/C genotype (Leu141) exhibited higher IFNAR1 protein expression levels in peripheral blood monocytes than those with the 19158G/G genotype (Val141). In conclusion, IFNAR1 19158C/G polymorphism is primarily associated with susceptibility to chronic HBV infection. © 2008 The Authors.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltden_HK
dc.relation.ispartofJournal of Viral Hepatitisen_HK
dc.rightsJournal of Viral Hepatitis. Copyright © Blackwell Publishing Ltd.en_HK
dc.subjectHBV infectionen_HK
dc.subjectIFNAR1en_HK
dc.subjectProtein stabilityen_HK
dc.subjectSNPen_HK
dc.subject.meshAmino Acid Substitution - geneticsen_HK
dc.subject.meshDisease Susceptibilityen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshHepatitis B, Chronic - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMutation, Missenseen_HK
dc.subject.meshPoint Mutationen_HK
dc.subject.meshPolymorphism, Restriction Fragment Lengthen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshReceptor, Interferon alpha-beta - biosynthesis - geneticsen_HK
dc.subject.meshSequence Analysis, DNAen_HK
dc.titleA non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infectionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1352-0504&volume=16&issue=1&spage=45&epage=52&date=2009&atitle=A+non-synonymous+single+nucleotide+polymorphism+in+IFNAR1+affects+susceptibility+to+chronic+hepatitis+B+virus+infectionen_HK
dc.identifier.emailZhou, J:jiezhou@hku.hken_HK
dc.identifier.emailLu, L:liweilu@hkucc.hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityZhou, J=rp01412en_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1365-2893.2008.01040.xen_HK
dc.identifier.pmid18761606-
dc.identifier.scopuseid_2-s2.0-58149083528en_HK
dc.identifier.hkuros156481en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58149083528&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume16en_HK
dc.identifier.issue1en_HK
dc.identifier.spage45en_HK
dc.identifier.epage52en_HK
dc.identifier.isiWOS:000261881300006-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZhou, J=7405550443en_HK
dc.identifier.scopusauthoridSmith, DK=7410351143en_HK
dc.identifier.scopusauthoridLu, L=7403963552en_HK
dc.identifier.scopusauthoridPoon, VKM=6603703384en_HK
dc.identifier.scopusauthoridNg, F=7103125273en_HK
dc.identifier.scopusauthoridChen, DQ=26634742000en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridCao, KY=15845100900en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.citeulike3830173-

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