Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS</title><author><name sortKey="Bartlett, Jaclyn R" sort="Bartlett, Jaclyn R" uniqKey="Bartlett J" first="Jaclyn R." last="Bartlett">Jaclyn R. Bartlett</name></author><author><name sortKey="Friedman, Kenneth J" sort="Friedman, Kenneth J" uniqKey="Friedman K" first="Kenneth J." last="Friedman">Kenneth J. Friedman</name></author><author><name sortKey="Ling, Simon C" sort="Ling, Simon C" uniqKey="Ling S" first="Simon C." last="Ling">Simon C. Ling</name></author><author><name sortKey="Pace, Rhonda G" sort="Pace, Rhonda G" uniqKey="Pace R" first="Rhonda G." last="Pace">Rhonda G. Pace</name></author><author><name sortKey="Bell, Scott C" sort="Bell, Scott C" uniqKey="Bell S" first="Scott C." last="Bell">Scott C. Bell</name></author><author><name sortKey="Bourke, Billy" sort="Bourke, Billy" uniqKey="Bourke B" first="Billy" last="Bourke">Billy Bourke</name></author><author><name sortKey="Castaldo, Giuseppe" sort="Castaldo, Giuseppe" uniqKey="Castaldo G" first="Giuseppe" last="Castaldo">Giuseppe Castaldo</name></author><author><name sortKey="Castellani, Carlo" sort="Castellani, Carlo" uniqKey="Castellani C" first="Carlo" last="Castellani">Carlo Castellani</name></author><author><name sortKey="Cipolli, Marco" sort="Cipolli, Marco" uniqKey="Cipolli M" first="Marco" last="Cipolli">Marco Cipolli</name></author><author><name sortKey="Colombo, Carla" sort="Colombo, Carla" uniqKey="Colombo C" first="Carla" last="Colombo">Carla Colombo</name></author><author><name sortKey="Colombo, John L" sort="Colombo, John L" uniqKey="Colombo J" first="John L." last="Colombo">John L. Colombo</name></author><author><name sortKey="Debray, Dominique" sort="Debray, Dominique" uniqKey="Debray D" first="Dominique" last="Debray">Dominique Debray</name></author><author><name sortKey="Fernandez, Adriana" sort="Fernandez, Adriana" uniqKey="Fernandez A" first="Adriana" last="Fernandez">Adriana Fernandez</name></author><author><name sortKey="Lacaille, Florence" sort="Lacaille, Florence" uniqKey="Lacaille F" first="Florence" last="Lacaille">Florence Lacaille</name></author><author><name sortKey="Macek, Milan" sort="Macek, Milan" uniqKey="Macek M" first="Milan" last="Macek">Milan Macek</name></author><author><name sortKey="Rowland, Marion" sort="Rowland, Marion" uniqKey="Rowland M" first="Marion" last="Rowland">Marion Rowland</name></author><author><name sortKey="Salvatore, Francesco" sort="Salvatore, Francesco" uniqKey="Salvatore F" first="Francesco" last="Salvatore">Francesco Salvatore</name></author><author><name sortKey="Taylor, Christopher J" sort="Taylor, Christopher J" uniqKey="Taylor C" first="Christopher J." last="Taylor">Christopher J. Taylor</name></author><author><name sortKey="Wainwright, Claire" sort="Wainwright, Claire" uniqKey="Wainwright C" first="Claire" last="Wainwright">Claire Wainwright</name></author><author><name sortKey="Wilschanski, Michael" sort="Wilschanski, Michael" uniqKey="Wilschanski M" first="Michael" last="Wilschanski">Michael Wilschanski</name></author><author><name sortKey="Zemkova, Dana" sort="Zemkova, Dana" uniqKey="Zemkova D" first="Dana" last="Zemková">Dana Zemková</name></author><author><name sortKey="Hannah, William B" sort="Hannah, William B" uniqKey="Hannah W" first="William B." last="Hannah">William B. Hannah</name></author><author><name sortKey="Phillips, M James" sort="Phillips, M James" uniqKey="Phillips M" first="M. James" last="Phillips">M. James Phillips</name></author><author><name sortKey="Corey, Mary" sort="Corey, Mary" uniqKey="Corey M" first="Mary" last="Corey">Mary Corey</name></author><author><name sortKey="Zielenski, Julian" sort="Zielenski, Julian" uniqKey="Zielenski J" first="Julian" last="Zielenski">Julian Zielenski</name></author><author><name sortKey="Dorfman, Ruslan" sort="Dorfman, Ruslan" uniqKey="Dorfman R" first="Ruslan" last="Dorfman">Ruslan Dorfman</name></author><author><name sortKey="Wang, Yunfei" sort="Wang, Yunfei" uniqKey="Wang Y" first="Yunfei" last="Wang">Yunfei Wang</name></author><author><name sortKey="Zou, Fei" sort="Zou, Fei" uniqKey="Zou F" first="Fei" last="Zou">Fei Zou</name></author><author><name sortKey="Silverman, Lawrence M" sort="Silverman, Lawrence M" uniqKey="Silverman L" first="Lawrence M." last="Silverman">Lawrence M. Silverman</name></author><author><name sortKey="Drumm, Mitchell L" sort="Drumm, Mitchell L" uniqKey="Drumm M" first="Mitchell L." last="Drumm">Mitchell L. Drumm</name></author><author><name sortKey="Wright, Fred A" sort="Wright, Fred A" uniqKey="Wright F" first="Fred A." last="Wright">Fred A. Wright</name></author><author><name sortKey="Lange, Ethan M" sort="Lange, Ethan M" uniqKey="Lange E" first="Ethan M." last="Lange">Ethan M. Lange</name></author><author><name sortKey="Durie, Peter R" sort="Durie, Peter R" uniqKey="Durie P" first="Peter R." last="Durie">Peter R. Durie</name></author><author><name sortKey="Knowles, Michael R" sort="Knowles, Michael R" uniqKey="Knowles M" first="Michael R." last="Knowles">Michael R. Knowles</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19738092</idno><idno type="pmc">3711243</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711243</idno><idno type="RBID">PMC:3711243</idno><idno type="doi">10.1001/jama.2009.1295</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001F37</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001F37</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS</title><author><name sortKey="Bartlett, Jaclyn R" sort="Bartlett, Jaclyn R" uniqKey="Bartlett J" first="Jaclyn R." last="Bartlett">Jaclyn R. Bartlett</name></author><author><name sortKey="Friedman, Kenneth J" sort="Friedman, Kenneth J" uniqKey="Friedman K" first="Kenneth J." last="Friedman">Kenneth J. Friedman</name></author><author><name sortKey="Ling, Simon C" sort="Ling, Simon C" uniqKey="Ling S" first="Simon C." last="Ling">Simon C. Ling</name></author><author><name sortKey="Pace, Rhonda G" sort="Pace, Rhonda G" uniqKey="Pace R" first="Rhonda G." last="Pace">Rhonda G. Pace</name></author><author><name sortKey="Bell, Scott C" sort="Bell, Scott C" uniqKey="Bell S" first="Scott C." last="Bell">Scott C. Bell</name></author><author><name sortKey="Bourke, Billy" sort="Bourke, Billy" uniqKey="Bourke B" first="Billy" last="Bourke">Billy Bourke</name></author><author><name sortKey="Castaldo, Giuseppe" sort="Castaldo, Giuseppe" uniqKey="Castaldo G" first="Giuseppe" last="Castaldo">Giuseppe Castaldo</name></author><author><name sortKey="Castellani, Carlo" sort="Castellani, Carlo" uniqKey="Castellani C" first="Carlo" last="Castellani">Carlo Castellani</name></author><author><name sortKey="Cipolli, Marco" sort="Cipolli, Marco" uniqKey="Cipolli M" first="Marco" last="Cipolli">Marco Cipolli</name></author><author><name sortKey="Colombo, Carla" sort="Colombo, Carla" uniqKey="Colombo C" first="Carla" last="Colombo">Carla Colombo</name></author><author><name sortKey="Colombo, John L" sort="Colombo, John L" uniqKey="Colombo J" first="John L." last="Colombo">John L. Colombo</name></author><author><name sortKey="Debray, Dominique" sort="Debray, Dominique" uniqKey="Debray D" first="Dominique" last="Debray">Dominique Debray</name></author><author><name sortKey="Fernandez, Adriana" sort="Fernandez, Adriana" uniqKey="Fernandez A" first="Adriana" last="Fernandez">Adriana Fernandez</name></author><author><name sortKey="Lacaille, Florence" sort="Lacaille, Florence" uniqKey="Lacaille F" first="Florence" last="Lacaille">Florence Lacaille</name></author><author><name sortKey="Macek, Milan" sort="Macek, Milan" uniqKey="Macek M" first="Milan" last="Macek">Milan Macek</name></author><author><name sortKey="Rowland, Marion" sort="Rowland, Marion" uniqKey="Rowland M" first="Marion" last="Rowland">Marion Rowland</name></author><author><name sortKey="Salvatore, Francesco" sort="Salvatore, Francesco" uniqKey="Salvatore F" first="Francesco" last="Salvatore">Francesco Salvatore</name></author><author><name sortKey="Taylor, Christopher J" sort="Taylor, Christopher J" uniqKey="Taylor C" first="Christopher J." last="Taylor">Christopher J. Taylor</name></author><author><name sortKey="Wainwright, Claire" sort="Wainwright, Claire" uniqKey="Wainwright C" first="Claire" last="Wainwright">Claire Wainwright</name></author><author><name sortKey="Wilschanski, Michael" sort="Wilschanski, Michael" uniqKey="Wilschanski M" first="Michael" last="Wilschanski">Michael Wilschanski</name></author><author><name sortKey="Zemkova, Dana" sort="Zemkova, Dana" uniqKey="Zemkova D" first="Dana" last="Zemková">Dana Zemková</name></author><author><name sortKey="Hannah, William B" sort="Hannah, William B" uniqKey="Hannah W" first="William B." last="Hannah">William B. Hannah</name></author><author><name sortKey="Phillips, M James" sort="Phillips, M James" uniqKey="Phillips M" first="M. James" last="Phillips">M. James Phillips</name></author><author><name sortKey="Corey, Mary" sort="Corey, Mary" uniqKey="Corey M" first="Mary" last="Corey">Mary Corey</name></author><author><name sortKey="Zielenski, Julian" sort="Zielenski, Julian" uniqKey="Zielenski J" first="Julian" last="Zielenski">Julian Zielenski</name></author><author><name sortKey="Dorfman, Ruslan" sort="Dorfman, Ruslan" uniqKey="Dorfman R" first="Ruslan" last="Dorfman">Ruslan Dorfman</name></author><author><name sortKey="Wang, Yunfei" sort="Wang, Yunfei" uniqKey="Wang Y" first="Yunfei" last="Wang">Yunfei Wang</name></author><author><name sortKey="Zou, Fei" sort="Zou, Fei" uniqKey="Zou F" first="Fei" last="Zou">Fei Zou</name></author><author><name sortKey="Silverman, Lawrence M" sort="Silverman, Lawrence M" uniqKey="Silverman L" first="Lawrence M." last="Silverman">Lawrence M. Silverman</name></author><author><name sortKey="Drumm, Mitchell L" sort="Drumm, Mitchell L" uniqKey="Drumm M" first="Mitchell L." last="Drumm">Mitchell L. Drumm</name></author><author><name sortKey="Wright, Fred A" sort="Wright, Fred A" uniqKey="Wright F" first="Fred A." last="Wright">Fred A. Wright</name></author><author><name sortKey="Lange, Ethan M" sort="Lange, Ethan M" uniqKey="Lange E" first="Ethan M." last="Lange">Ethan M. Lange</name></author><author><name sortKey="Durie, Peter R" sort="Durie, Peter R" uniqKey="Durie P" first="Peter R." last="Durie">Peter R. Durie</name></author><author><name sortKey="Knowles, Michael R" sort="Knowles, Michael R" uniqKey="Knowles M" first="Michael R." last="Knowles">Michael R. Knowles</name></author></analytic><series><title level="j">JAMA : the journal of the American Medical Association</title><idno type="ISSN">0098-7484</idno><idno type="eISSN">1538-3598</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Context</title><p id="P2">A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension.</p></sec><sec id="S2"><title>Objective</title><p id="P3">To assess whether any of 9 polymorphisms in 5 candidate genes (<italic>SERPINA1, ACE, GSTP1, MBL2</italic>, and <italic>TGFB1</italic>) are associated with severe liver disease in CF patients.</p></sec><sec id="S3"><title>Design, Setting, and Participants</title><p id="P4">A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the <italic>SERPINA1</italic> Z allele and <italic>TGFB1</italic> codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls.</p></sec><sec id="S4"><title>Main Outcome Measures</title><p id="P5">We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD.</p></sec><sec id="S5"><title>Results</title><p id="P6">The initial study showed CFLD to be associated with the <italic>SERPINA1</italic> (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10<sup>−6</sup>; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (<italic>TGFB1</italic>) codon 10 CC genotype (P=2.8×10<sup>−3</sup>; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the <italic>SERPINA1</italic> Z allele (P=1.4×10<sup>−3</sup>; OR 3.42, CI 1.54–7.59), but not with <italic>TGFB1</italic> codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with <italic>SERPINA1</italic> Z allele (P=1.5×10<sup>−8</sup>; OR 5.04, CI 2.88–8.83).</p></sec><sec id="S6"><title>Conclusion</title><p id="P7">The <italic>SERPINA1</italic> Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7501160</journal-id><journal-id journal-id-type="pubmed-jr-id">5346</journal-id><journal-id journal-id-type="nlm-ta">JAMA</journal-id><journal-id journal-id-type="iso-abbrev">JAMA</journal-id><journal-title-group><journal-title>JAMA : the journal of the American Medical Association</journal-title></journal-title-group><issn pub-type="ppub">0098-7484</issn><issn pub-type="epub">1538-3598</issn></journal-meta><article-meta><article-id pub-id-type="pmid">19738092</article-id><article-id pub-id-type="pmc">3711243</article-id><article-id pub-id-type="doi">10.1001/jama.2009.1295</article-id><article-id pub-id-type="manuscript">NIHMS254899</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bartlett</surname><given-names>Jaclyn R.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Friedman</surname><given-names>Kenneth J.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Ling</surname><given-names>Simon C.</given-names></name><degrees>MB, ChB</degrees></contrib><contrib contrib-type="author"><name><surname>Pace</surname><given-names>Rhonda G.</given-names></name><degrees>BS</degrees></contrib><contrib contrib-type="author"><name><surname>Bell</surname><given-names>Scott C.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Bourke</surname><given-names>Billy</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Castaldo</surname><given-names>Giuseppe</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Castellani</surname><given-names>Carlo</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Cipolli</surname><given-names>Marco</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Colombo</surname><given-names>Carla</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Colombo</surname><given-names>John L.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Debray</surname><given-names>Dominique</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Fernandez</surname><given-names>Adriana</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Lacaille</surname><given-names>Florence</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Macek</surname><given-names>Milan</given-names><suffix>Jr.</suffix></name><degrees>MD, DSc</degrees></contrib><contrib contrib-type="author"><name><surname>Rowland</surname><given-names>Marion</given-names></name><degrees>MB, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Salvatore</surname><given-names>Francesco</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Taylor</surname><given-names>Christopher J.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Wainwright</surname><given-names>Claire</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Wilschanski</surname><given-names>Michael</given-names></name><degrees>MBBS</degrees></contrib><contrib contrib-type="author"><name><surname>Zemková</surname><given-names>Dana</given-names></name><degrees>CSc</degrees></contrib><contrib contrib-type="author"><name><surname>Hannah</surname><given-names>William B.</given-names></name><degrees>BS</degrees></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>M. James</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Corey</surname><given-names>Mary</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Zielenski</surname><given-names>Julian</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Dorfman</surname><given-names>Ruslan</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yunfei</given-names></name><degrees>MS</degrees></contrib><contrib contrib-type="author"><name><surname>Zou</surname><given-names>Fei</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Silverman</surname><given-names>Lawrence M.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Drumm</surname><given-names>Mitchell L.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Wright</surname><given-names>Fred A.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Lange</surname><given-names>Ethan M.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Durie</surname><given-names>Peter R.</given-names></name><degrees>MD</degrees><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Knowles</surname><given-names>Michael R.</given-names></name><degrees>MD</degrees><xref ref-type="author-notes" rid="FN1">*</xref><on-behalf-of>for the Gene Modifier Study Group</on-behalf-of></contrib><aff id="A1">Cystic Fibrosis/Pulmonary Research and Treatment Center (Drs Bartlett and Knowles, Ms Pace, and Mr Hannah) and Department of Genetics (Dr Lange and Mr Wang), School of Medicine, and Department of Biostatistics, School of Public Health (Drs Zou, Wright, and Lange, and Mr Wang), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Molecular Biology and Pathology, Laboratory Corporation of America, Research Triangle Park, North Carolina (Dr Friedman); Division of Gastroenterology, Hepatology and Nutrition (Drs Ling and Durie), Pediatric Laboratory Medicine (Dr Phillips), Child Health Evaluative Sciences (Dr Corey), Genetics and Genome Biology (Drs Zielenski and Dorfman), and Physiology and Experimental Medicine (Dr Durie), The Hospital for Sick Children, and the University of Toronto (Drs Ling, Corey, and Durie), Toronto, Canada; Adult Cystic Fibrosis Centre, Prince Charles Hospital, Chermside, Queensland, Australia (Dr Bell); Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin (Drs Bourke and Rowland) and University College Dublin School of Medicine and Medical Science (Dr Rowland), Dublin, Ireland; CEINGE-Advanced Biotechnologies and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy (Drs Castaldo and Salvatore); Cystic Fibrosis Centre, Azienda Ospedaliera di Verona, Verona, Italy (Drs Castellani and Cipolli); CF Center, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy (Dr C. Colombo); Department of Pediatrics, Pulmonary Section, University of Nebraska Medical Center, Omaha, Nebraska (Dr J. Colombo); Service d'Hépatologie Pédiatrique, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin- Bicêtre Cedex, France (Dr Debray); Cystic Fibrosis Center, La Plata Children’s Hospital, La Plata, Buenos Aires, Argentina (Dr Fernandez); the Pediatric Hepato-Gastroenterology-Nutrition Unit, Necker-Enfants Malades Hospital, Paris, France (Dr. Lacaille); Departments of Biology and Medical Genetics (Dr Macek) and Pediatrics (Ms Zemková), Charles University and University Hospital Motol, Prague, Czech Republic; Department of Paediatric Gastroenterology, Academic Unit of Child Health, University of Sheffield, Sheffield, United Kingdom (Dr Taylor); Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, Queensland, Australia (Dr Wainwright); Department of Pediatric Gastroenterology, Hadassah Medical Organization, Jerusalem, Israel (Dr Wilschanski); Department of Pathology, University of Virginia, Charlottesville, Virginia (Dr Silverman); and Departments of Pediatrics and Genetics, Case Western Reserve University, Cleveland, Ohio (Dr Drumm).</aff></contrib-group><author-notes><corresp id="cor1"><bold>Corresponding Author</bold>: Michael R. Knowles, MD, Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 7019 Thurston-Bowles Bldg., CB# 7248, Chapel Hill, NC 27599 (<email>knowles@med.unc.edu</email>)</corresp><fn id="FN1"><label>*</label><p id="P1">These authors jointly directed the project.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>6</day><month>6</month><year>2013</year></pub-date><pub-date pub-type="ppub"><day>9</day><month>9</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>7</month><year>2013</year></pub-date><volume>302</volume><issue>10</issue><fpage>1076</fpage><lpage>1083</lpage><abstract><sec id="S1"><title>Context</title><p id="P2">A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension.</p></sec><sec id="S2"><title>Objective</title><p id="P3">To assess whether any of 9 polymorphisms in 5 candidate genes (<italic>SERPINA1, ACE, GSTP1, MBL2</italic>, and <italic>TGFB1</italic>) are associated with severe liver disease in CF patients.</p></sec><sec id="S3"><title>Design, Setting, and Participants</title><p id="P4">A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the <italic>SERPINA1</italic> Z allele and <italic>TGFB1</italic> codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls.</p></sec><sec id="S4"><title>Main Outcome Measures</title><p id="P5">We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD.</p></sec><sec id="S5"><title>Results</title><p id="P6">The initial study showed CFLD to be associated with the <italic>SERPINA1</italic> (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10<sup>−6</sup>; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (<italic>TGFB1</italic>) codon 10 CC genotype (P=2.8×10<sup>−3</sup>; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the <italic>SERPINA1</italic> Z allele (P=1.4×10<sup>−3</sup>; OR 3.42, CI 1.54–7.59), but not with <italic>TGFB1</italic> codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with <italic>SERPINA1</italic> Z allele (P=1.5×10<sup>−8</sup>; OR 5.04, CI 2.88–8.83).</p></sec><sec id="S6"><title>Conclusion</title><p id="P7">The <italic>SERPINA1</italic> Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension.</p></sec></abstract><funding-group><award-group><funding-source country="United States">National Heart, Lung, and Blood Institute : NHLBI</funding-source><award-id>R21 HL079093-02 || HL</award-id></award-group><award-group><funding-source country="United States">National Heart, Lung, and Blood Institute : NHLBI</funding-source><award-id>R21 HL079093-01 || HL</award-id></award-group><award-group><funding-source country="United States">National Heart, Lung, and Blood Institute : NHLBI</funding-source><award-id>R01 HL068890 || HL</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001F37 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001F37 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |