Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein (AHSG) Gene Associated with the Risk of SARS-CoV Infection
Identifieur interne : 001372 ( Pmc/Curation ); précédent : 001371; suivant : 001373Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein (AHSG) Gene Associated with the Risk of SARS-CoV Infection
Auteurs : Xiaohui Zhu [République populaire de Chine] ; Yan Wang [République populaire de Chine] ; Hongxing Zhang [République populaire de Chine] ; Xuan Liu [République populaire de Chine] ; Ting Chen [République populaire de Chine] ; Ruifu Yang [République populaire de Chine] ; Yuling Shi [République populaire de Chine] ; Wuchun Cao [République populaire de Chine] ; Ping Li [République populaire de Chine] ; Qingjun Ma [République populaire de Chine] ; Yun Zhai [République populaire de Chine] ; Fuchu He [République populaire de Chine] ; Gangqiao Zhou [République populaire de Chine] ; Cheng Cao [République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Genetic background may play an important role in the process of SARS-CoV
infection and SARS development. We found several proteins that could interact
with the nucleocapsid protein of the SARS coronavirus (SARS-CoV).
α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage
deactivation by endogenous cations, is associated with inflammatory regulation.
Cytochrome P450 Family 3A (CYP4F3A) is an
Url:
DOI: 10.1371/journal.pone.0023730
PubMed: 21904596
PubMed Central: 3163911
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id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Ma, Qingjun" sort="Ma, Qingjun" uniqKey="Ma Q" first="Qingjun" last="Ma">Qingjun Ma</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhai, Yun" sort="Zhai, Yun" uniqKey="Zhai Y" first="Yun" last="Zhai">Yun Zhai</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="He, Fuchu" sort="He, Fuchu" uniqKey="He F" first="Fuchu" last="He">Fuchu He</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Gangqiao" sort="Zhou, Gangqiao" uniqKey="Zhou G" first="Gangqiao" last="Zhou">Gangqiao Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Cheng" sort="Cao, Cheng" uniqKey="Cao C" first="Cheng" last="Cao">Cheng Cao</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21904596</idno><idno type="pmc">3163911</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163911</idno><idno type="RBID">PMC:3163911</idno><idno type="doi">10.1371/journal.pone.0023730</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001372</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001372</idno><idno type="wicri:Area/Pmc/Curation">001372</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001372</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein
(AHSG) Gene Associated with the Risk of SARS-CoV Infection</title><author><name sortKey="Zhu, Xiaohui" sort="Zhu, Xiaohui" uniqKey="Zhu X" first="Xiaohui" last="Zhu">Xiaohui Zhu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yan" sort="Wang, Yan" uniqKey="Wang Y" first="Yan" last="Wang">Yan Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>General Hospital of Beijing Command, PLA, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>General Hospital of Beijing Command, PLA, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Hongxing" sort="Zhang, Hongxing" uniqKey="Zhang H" first="Hongxing" last="Zhang">Hongxing Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Xuan" sort="Liu, Xuan" uniqKey="Liu X" first="Xuan" last="Liu">Xuan Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Ting" sort="Chen, Ting" uniqKey="Chen T" first="Ting" last="Chen">Ting Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Ruifu" sort="Yang, Ruifu" uniqKey="Yang R" first="Ruifu" last="Yang">Ruifu Yang</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Institute of Microbiology and Epidemiology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Yuling" sort="Shi, Yuling" uniqKey="Shi Y" first="Yuling" last="Shi">Yuling Shi</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>General Hospital of Guangzhou Command, PLA, Guangzhou, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>General Hospital of Guangzhou Command, PLA, Guangzhou</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Wuchun" sort="Cao, Wuchun" uniqKey="Cao W" first="Wuchun" last="Cao">Wuchun Cao</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Institute of Microbiology and Epidemiology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Li, Ping" sort="Li, Ping" uniqKey="Li P" first="Ping" last="Li">Ping Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Ma, Qingjun" sort="Ma, Qingjun" uniqKey="Ma Q" first="Qingjun" last="Ma">Qingjun Ma</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhai, Yun" sort="Zhai, Yun" uniqKey="Zhai Y" first="Yun" last="Zhai">Yun Zhai</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="He, Fuchu" sort="He, Fuchu" uniqKey="He F" first="Fuchu" last="He">Fuchu He</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Gangqiao" sort="Zhou, Gangqiao" uniqKey="Zhou G" first="Gangqiao" last="Zhou">Gangqiao Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Research Center for Protein Drugs, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Cheng" sort="Cao, Cheng" uniqKey="Cao C" first="Cheng" last="Cao">Cheng Cao</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Genetic background may play an important role in the process of SARS-CoV
infection and SARS development. We found several proteins that could interact
with the nucleocapsid protein of the SARS coronavirus (SARS-CoV).
α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage
deactivation by endogenous cations, is associated with inflammatory regulation.
Cytochrome P450 Family 3A (CYP4F3A) is an <italic>ω</italic>-oxidase that
inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We
investigated the association between the polymorphisms of these two
inflammation-associated genes and SARS development. The linkage disequilibrium
(LD) maps of these two genes were built with Haploview using data on
CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected
and genotyped. In the Guangzhou cohort study, after adjusting for age and sex,
two <italic>AHSG</italic> SNPs and one <italic>CYP4F3</italic> SNP were found to
be associated with SARS susceptibility: rs2248690 (adjusted odds ratio
[AOR] 2.42; 95% confidence interval [CI] 1.30-4.51);
rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95%
CI 1.10–3.68). To further validate the association, the ten tag SNPs were
genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690
(AOR, 1.63; 95% CI, 1.30–2.04) was found to be associated with SARS
susceptibility. The combined analysis of the two studies confirmed tag SNP
rs2248690 in <italic>AHSG</italic> as a susceptibility variant (AOR 1.70;
95% CI 1.37–2.09). The statistical analysis of the rs2248690
genotype data among the patients and healthy controls in the HCW cohort, who
were all similarly exposed to the SARS virus, also supported the findings.
Further, the SNP rs2248690 affected the transcriptional activity of the
<italic>AHSG</italic> promoter and thus regulated the AHSG serum level.
Therefore, our study has demonstrated that the AA genotype of rs2268690, which
leads to a higher AHSG serum concentration, was significantly associated with
protection against SARS development.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Lai, St" uniqKey="Lai S">ST Lai</name></author><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yam, Ly" uniqKey="Yam L">LY Yam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name></author><author><name sortKey="Goldsmith, Cs" uniqKey="Goldsmith C">CS Goldsmith</name></author><author><name sortKey="Zaki, Sr" uniqKey="Zaki S">SR Zaki</name></author><author><name sortKey="Peret, T" uniqKey="Peret T">T Peret</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21904596</article-id><article-id pub-id-type="pmc">3163911</article-id><article-id pub-id-type="publisher-id">PONE-D-11-03160</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0023730</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Glycobiology</subject><subj-group><subject>Glycoproteins</subject></subj-group></subj-group></subj-group><subj-group><subject>Genetics</subject><subj-group><subject>Human Genetics</subject><subj-group><subject>Genetic Association Studies</subject></subj-group></subj-group><subj-group><subject>Population Genetics</subject><subj-group><subject>Genetic Polymorphism</subject></subj-group></subj-group><subj-group><subject>Genetic Mutation</subject></subj-group></subj-group><subj-group><subject>Immunology</subject><subj-group><subject>Immunity</subject><subj-group><subject>Inflammation</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Clinical Genetics</subject></subj-group><subj-group><subject>Clinical Immunology</subject><subj-group><subject>Immunity</subject><subj-group><subject>Inflammation</subject></subj-group></subj-group></subj-group><subj-group><subject>Clinical Research Design</subject><subj-group><subject>Cohort Studies</subject></subj-group></subj-group><subj-group><subject>Epidemiology</subject></subj-group><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject><subj-group><subject>SARS</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein
(AHSG) Gene Associated with the Risk of SARS-CoV Infection</article-title><alt-title alt-title-type="running-head">Variation of the AHSG Gene Associated with
SARS</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhu</surname><given-names>Xiaohui</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Wang</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhang</surname><given-names>Hongxing</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Liu</surname><given-names>Xuan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Ting</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Ruifu</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Yuling</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Wuchun</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Ping</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Qingjun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhai</surname><given-names>Yun</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Fuchu</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Gangqiao</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Cheng</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>State Key Laboratory of Pathogen and Bio-Security, Beijing Institute of Biotechnology, Beijing, China</addr-line></aff><aff id="aff2"><label>2</label><addr-line>State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China</addr-line></aff><aff id="aff3"><label>3</label><addr-line>State Key Laboratory of Pathogen and Bio-Security, Institute of Microbiology and Epidemiology, Beijing, China</addr-line></aff><aff id="aff4"><label>4</label><addr-line>General Hospital of Guangzhou Command, PLA, Guangzhou, China</addr-line></aff><aff id="aff5"><label>5</label><addr-line>General Hospital of Beijing Command, PLA, Beijing, China</addr-line></aff><aff id="aff6"><label>6</label><addr-line>National Engineering Research Center for Protein Drugs, Beijing, China</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Thiel</surname><given-names>Volker</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Kantonal Hospital St. Gallen, Switzerland</aff><author-notes><corresp id="cor1">* E-mail: <email>zhougq114@gmail.com</email> (GZ); <email>caoc@nic.bmi.ac.cn</email> (CC)</corresp><fn fn-type="con"><p>Conceived and designed the experiments: QM GZ CC. Performed the experiments:
YW XZ XL PL TC. Analyzed the data: XZ YW HZ. Contributed
reagents/materials/analysis tools: HZ YZ RY YS WC FH. Wrote the paper: XZ YW
CC.</p></fn></author-notes><pub-date pub-type="collection"><year>2011</year></pub-date><pub-date pub-type="epub"><day>17</day><month>8</month><year>2011</year></pub-date><volume>6</volume><issue>8</issue><elocation-id>e23730</elocation-id><history><date date-type="received"><day>13</day><month>2</month><year>2011</year></date><date date-type="accepted"><day>26</day><month>7</month><year>2011</year></date></history><permissions><copyright-statement>Zhu et al.</copyright-statement><copyright-year>2011</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>Genetic background may play an important role in the process of SARS-CoV
infection and SARS development. We found several proteins that could interact
with the nucleocapsid protein of the SARS coronavirus (SARS-CoV).
α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage
deactivation by endogenous cations, is associated with inflammatory regulation.
Cytochrome P450 Family 3A (CYP4F3A) is an <italic>ω</italic>-oxidase that
inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We
investigated the association between the polymorphisms of these two
inflammation-associated genes and SARS development. The linkage disequilibrium
(LD) maps of these two genes were built with Haploview using data on
CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected
and genotyped. In the Guangzhou cohort study, after adjusting for age and sex,
two <italic>AHSG</italic> SNPs and one <italic>CYP4F3</italic> SNP were found to
be associated with SARS susceptibility: rs2248690 (adjusted odds ratio
[AOR] 2.42; 95% confidence interval [CI] 1.30-4.51);
rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95%
CI 1.10–3.68). To further validate the association, the ten tag SNPs were
genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690
(AOR, 1.63; 95% CI, 1.30–2.04) was found to be associated with SARS
susceptibility. The combined analysis of the two studies confirmed tag SNP
rs2248690 in <italic>AHSG</italic> as a susceptibility variant (AOR 1.70;
95% CI 1.37–2.09). The statistical analysis of the rs2248690
genotype data among the patients and healthy controls in the HCW cohort, who
were all similarly exposed to the SARS virus, also supported the findings.
Further, the SNP rs2248690 affected the transcriptional activity of the
<italic>AHSG</italic> promoter and thus regulated the AHSG serum level.
Therefore, our study has demonstrated that the AA genotype of rs2268690, which
leads to a higher AHSG serum concentration, was significantly associated with
protection against SARS development.</p></abstract><counts><page-count count="8"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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