GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS
Identifieur interne : 007C10 ( Main/Exploration ); précédent : 007C09; suivant : 007C11GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS
Auteurs : Jaclyn R. Bartlett ; Kenneth J. Friedman ; Simon C. Ling ; Rhonda G. Pace ; Scott C. Bell ; Billy Bourke ; Giuseppe Castaldo ; Carlo Castellani ; Marco Cipolli ; Carla Colombo ; John L. Colombo ; Dominique Debray ; Adriana Fernandez ; Florence Lacaille ; Milan Macek ; Marion Rowland ; Francesco Salvatore ; Christopher J. Taylor ; Claire Wainwright ; Michael Wilschanski ; Dana Zemková ; William B. Hannah ; M. James Phillips ; Mary Corey ; Julian Zielenski ; Ruslan Dorfman ; Yunfei Wang ; Fei Zou ; Lawrence M. Silverman ; Mitchell L. Drumm ; Fred A. Wright ; Ethan M. Lange ; Peter R. Durie ; Michael R. KnowlesSource :
- JAMA : the journal of the American Medical Association [ 0098-7484 ] ; 2009.
Abstract
A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension.
To assess whether any of 9 polymorphisms in 5 candidate genes (
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
We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD.
The initial study showed CFLD to be associated with the
The
Url:
DOI: 10.1001/jama.2009.1295
PubMed: 19738092
PubMed Central: 3711243
Affiliations:
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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><idno type="wicri:Area/Pmc/Curation">001D91</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001D91</idno><idno type="wicri:Area/Pmc/Checkpoint">002802</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002802</idno><idno type="wicri:Area/Ncbi/Merge">000641</idno><idno type="wicri:Area/Ncbi/Curation">000641</idno><idno type="wicri:Area/Ncbi/Checkpoint">000641</idno><idno type="wicri:doubleKey">0098-7484:2009:Bartlett J:genetic:modifiers:of</idno><idno type="wicri:Area/Main/Merge">008284</idno><idno type="wicri:Area/Main/Curation">007C10</idno><idno type="wicri:Area/Main/Exploration">007C10</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><affiliations><list></list><tree><noCountry><name sortKey="Bartlett, Jaclyn R" sort="Bartlett, Jaclyn R" uniqKey="Bartlett J" first="Jaclyn R." last="Bartlett">Jaclyn R. Bartlett</name><name sortKey="Bell, Scott C" sort="Bell, Scott C" uniqKey="Bell S" first="Scott C." last="Bell">Scott C. Bell</name><name sortKey="Bourke, Billy" sort="Bourke, Billy" uniqKey="Bourke B" first="Billy" last="Bourke">Billy Bourke</name><name sortKey="Castaldo, Giuseppe" sort="Castaldo, Giuseppe" uniqKey="Castaldo G" first="Giuseppe" last="Castaldo">Giuseppe Castaldo</name><name sortKey="Castellani, Carlo" sort="Castellani, Carlo" uniqKey="Castellani C" first="Carlo" last="Castellani">Carlo Castellani</name><name sortKey="Cipolli, Marco" sort="Cipolli, Marco" uniqKey="Cipolli M" first="Marco" last="Cipolli">Marco Cipolli</name><name sortKey="Colombo, Carla" sort="Colombo, Carla" uniqKey="Colombo C" first="Carla" last="Colombo">Carla Colombo</name><name sortKey="Colombo, John L" sort="Colombo, John L" uniqKey="Colombo J" first="John L." last="Colombo">John L. Colombo</name><name sortKey="Corey, Mary" sort="Corey, Mary" uniqKey="Corey M" first="Mary" last="Corey">Mary Corey</name><name sortKey="Debray, Dominique" sort="Debray, Dominique" uniqKey="Debray D" first="Dominique" last="Debray">Dominique Debray</name><name sortKey="Dorfman, Ruslan" sort="Dorfman, Ruslan" uniqKey="Dorfman R" first="Ruslan" last="Dorfman">Ruslan Dorfman</name><name sortKey="Drumm, Mitchell L" sort="Drumm, Mitchell L" uniqKey="Drumm M" first="Mitchell L." last="Drumm">Mitchell L. Drumm</name><name sortKey="Durie, Peter R" sort="Durie, Peter R" uniqKey="Durie P" first="Peter R." last="Durie">Peter R. Durie</name><name sortKey="Fernandez, Adriana" sort="Fernandez, Adriana" uniqKey="Fernandez A" first="Adriana" last="Fernandez">Adriana Fernandez</name><name sortKey="Friedman, Kenneth J" sort="Friedman, Kenneth J" uniqKey="Friedman K" first="Kenneth J." last="Friedman">Kenneth J. Friedman</name><name sortKey="Hannah, William B" sort="Hannah, William B" uniqKey="Hannah W" first="William B." last="Hannah">William B. Hannah</name><name sortKey="Knowles, Michael R" sort="Knowles, Michael R" uniqKey="Knowles M" first="Michael R." last="Knowles">Michael R. Knowles</name><name sortKey="Lacaille, Florence" sort="Lacaille, Florence" uniqKey="Lacaille F" first="Florence" last="Lacaille">Florence Lacaille</name><name sortKey="Lange, Ethan M" sort="Lange, Ethan M" uniqKey="Lange E" first="Ethan M." last="Lange">Ethan M. Lange</name><name sortKey="Ling, Simon C" sort="Ling, Simon C" uniqKey="Ling S" first="Simon C." last="Ling">Simon C. Ling</name><name sortKey="Macek, Milan" sort="Macek, Milan" uniqKey="Macek M" first="Milan" last="Macek">Milan Macek</name><name sortKey="Pace, Rhonda G" sort="Pace, Rhonda G" uniqKey="Pace R" first="Rhonda G." last="Pace">Rhonda G. Pace</name><name sortKey="Phillips, M James" sort="Phillips, M James" uniqKey="Phillips M" first="M. James" last="Phillips">M. James Phillips</name><name sortKey="Rowland, Marion" sort="Rowland, Marion" uniqKey="Rowland M" first="Marion" last="Rowland">Marion Rowland</name><name sortKey="Salvatore, Francesco" sort="Salvatore, Francesco" uniqKey="Salvatore F" first="Francesco" last="Salvatore">Francesco Salvatore</name><name sortKey="Silverman, Lawrence M" sort="Silverman, Lawrence M" uniqKey="Silverman L" first="Lawrence M." last="Silverman">Lawrence M. Silverman</name><name sortKey="Taylor, Christopher J" sort="Taylor, Christopher J" uniqKey="Taylor C" first="Christopher J." last="Taylor">Christopher J. Taylor</name><name sortKey="Wainwright, Claire" sort="Wainwright, Claire" uniqKey="Wainwright C" first="Claire" last="Wainwright">Claire Wainwright</name><name sortKey="Wang, Yunfei" sort="Wang, Yunfei" uniqKey="Wang Y" first="Yunfei" last="Wang">Yunfei Wang</name><name sortKey="Wilschanski, Michael" sort="Wilschanski, Michael" uniqKey="Wilschanski M" first="Michael" last="Wilschanski">Michael Wilschanski</name><name sortKey="Wright, Fred A" sort="Wright, Fred A" uniqKey="Wright F" first="Fred A." last="Wright">Fred A. Wright</name><name sortKey="Zemkova, Dana" sort="Zemkova, Dana" uniqKey="Zemkova D" first="Dana" last="Zemková">Dana Zemková</name><name sortKey="Zielenski, Julian" sort="Zielenski, Julian" uniqKey="Zielenski J" first="Julian" last="Zielenski">Julian Zielenski</name><name sortKey="Zou, Fei" sort="Zou, Fei" uniqKey="Zou F" first="Fei" last="Zou">Fei Zou</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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