Skip Navigation


Human Molecular Genetics Advance Access originally published online on June 2, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
13/15/1649    most recent
ddh171v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (40)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Celedón, J. C.
Right arrow Articles by Silverman, E. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Celedón, J. C.
Right arrow Articles by Silverman, E. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2004, Vol. 13, No. 15 1649-1656
DOI: 10.1093/hmg/ddh171
Human Molecular Genetics, Vol. 13, No. 15 © Oxford University Press 2004; all rights reserved

The transforming growth factor-ß1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD)

Juan C. Celedón1,2,3,*, Christoph Lange4, Benjamin A. Raby1,2,3, Augusto A. Litonjua1,2,3, Lyle J. Palmer1,3,5, Dawn L. DeMeo1,3,6, John J. Reilly3,6, David J. Kwiatkowski1,3, Harold A. Chapman7, Nan Laird4, Jody S. Sylvia1, Melvin Hernandez1, Frank E. Speizer1,3, Scott T. Weiss1,3 and Edwin K. Silverman1,3,6

1Channing Laboratory and 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, 3Harvard Medical School, Boston, MA, USA, 4Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA, 5Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth, Australia and 7Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA

Received April 6, 2004; Accepted May 19, 2004

Although cigarette smoking is the primary environmental risk factor, genetic risk factors likely influence the development of chronic obstructive pulmonary disease (COPD). Linkage analysis between short-tandem repeat markers on chromosome 19 and COPD phenotypes was followed by association analysis of single nucleotide polymorphisms in a gene on chromosome 19q [transforming growth factor-ß1 (TGFB1)] and COPD phenotypes in a family-based sample and a case–control study (cases with severe COPD and control subjects with significant history of smoking but no COPD). Stratification by smoking status substantially improved the evidence of linkage to chromosome 19q for COPD phenotypes. Among former and current smokers in the Boston Early-Onset COPD Study, there was significant evidence of linkage between chromosome 19q and pre-bronchodilator (pre-BD) FEV1 (LOD=3.30) and suggestive evidence of linkage between chromosome 19q and other COPD phenotypes. In these families, a SNP in the promoter region of TGFB1 (rs2241712) and two SNPs in the 3' genomic region of TGFB1 (rs2241718 and rs6957) were significantly associated with pre- and post-BD FEV1 (P<0.05). Among smokers in the COPD cases and control subjects, two SNPs in the promoter region of TGFB1 (rs2241712 and rs1800469) and one SNP in exon 1 of TGFB1 (rs1982073) were significantly associated with COPD (P≤0.02 in all cases). Chromosome 19q likely contains a genetic locus (or loci) that influences COPD through an interaction with cigarette smoking. We hypothesize that genetic variants in or near the TGFB1 gene influence the pathogenesis of COPD among cigarette smokers.

* To whom correspondence should be addressed at: Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA. Tel: +1 6175250856; Fax: +1 6175250958; Email: juan.celedon{at}channing.harvard.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
L. A. Bremer, S. M. Blackman, L. L. Vanscoy, K. E. McDougal, A. Bowers, K. M. Naughton, D. J. Cutler, and G. R. Cutting
Interaction between a novel TGFB1 haplotype and CFTR genotype is associated with improved lung function in cystic fibrosis
Hum. Mol. Genet., July 15, 2008; 17(14): 2228 - 2237.
[Abstract] [Full Text] [PDF]

Home page
 Therapeutic Advances in Respiratory DiseaseHome page
A. Zanini, A. Chetta, and D. Olivieri
Review: Therapeutic perspectives in bronchial vascular remodeling in COPD
Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 179 - 187.
[Abstract] [PDF]

Home page
 Proc Am Thorac SocHome page
C. P. Hersh, D. L. DeMeo, and E. K. Silverman
National Emphysema Treatment Trial State of the Art: Genetics of Emphysema
Proceedings of the ATS, May 1, 2008; 5(4): 486 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. M. Brehm and J. C. Celedon
Chronic Obstructive Pulmonary Disease in Hispanics
Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 473 - 478.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
J. M. Collaco, L. Vanscoy, L. Bremer, K. McDougal, S. M. Blackman, A. Bowers, K. Naughton, J. Jennings, J. Ellen, and G. R. Cutting
Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease
JAMA, January 30, 2008; 299(4): 417 - 424.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. L. DeMeo, E. J. Campbell, A. F. Barker, M. L. Brantly, E. Eden, N. G. McElvaney, S. I. Rennard, R. A. Sandhaus, J. M. Stocks, J. K. Stoller, et al.
IL10 Polymorphisms Are Associated with Airflow Obstruction in Severe {alpha}1-Antitrypsin Deficiency
Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 114 - 120.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. C. Jonth, L. Silveira, T. E. Fingerlin, H. Sato, J. C. Luby, K. I. Welsh, C. S. Rose, L. S. Newman, R. M. du Bois, L. A. Maier, et al.
TGF-beta1 Variants in Chronic Beryllium Disease and Sarcoidosis
J. Immunol., September 15, 2007; 179(6): 4255 - 4262.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. L. DeMeo, C. P. Hersh, E. A. Hoffman, A. A. Litonjua, R. Lazarus, D. Sparrow, J. O. Benditt, G. Criner, B. Make, F. J. Martinez, et al.
Genetic Determinants of Emphysema Distribution in the National Emphysema Treatment Trial
Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 42 - 48.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
H.-R. Kang, C. G. Lee, R. J. Homer, and J. A. Elias
Semaphorin 7A plays a critical role in TGF-{beta}1-induced pulmonary fibrosis
J. Exp. Med., May 14, 2007; 204(5): 1083 - 1093.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C. P. Hersh, D. T. Miller, D. J. Kwiatkowski, and E. K. Silverman
Genetic determinants of C-reactive protein in COPD
Eur. Respir. J., December 1, 2006; 28(6): 1156 - 1162.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
B. Beghe, E. Bazzan, S. Baraldo, F. Calabrese, F. Rea, M. Loy, P. Maestrelli, R. Zuin, L. M. Fabbri, and M. Saetta
Transforming growth factor-{beta} type II receptor in pulmonary arteries of patients with very severe COPD
Eur. Respir. J., September 1, 2006; 28(3): 556 - 562.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
W. O. C. Cookson
State of the Art. Genetics and Genomics of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, August 1, 2006; 3(6): 473 - 475.
[Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
E. K. Silverman
Progress in chronic obstructive pulmonary disease genetics.
Proceedings of the ATS, July 1, 2006; 3(5): 405 - 408.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. P. Hersh, D. L. DeMeo, R. Lazarus, J. C. Celedon, B. A. Raby, J. O. Benditt, G. Criner, B. Make, F. J. Martinez, P. D. Scanlon, et al.
Genetic Association Analysis of Functional Impairment in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 977 - 984.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
F. Stanke, B. Tummler, T. Becker, G. Rossi, V. Rossi, M. Drumm, F. Wright, and M. Knowles
Genetic Modifiers in Cystic Fibrosis
N. Engl. J. Med., January 5, 2006; 354(1): 88 - 90.
[Full Text] [PDF]

Home page
 ThoraxHome page
S Baraldo, E Bazzan, G Turato, F Calabrese, B Beghe, A Papi, P Maestrelli, L M Fabbri, R Zuin, and M Saetta
Decreased expression of TGF-{beta} type II receptor in bronchial glands of smokers with COPD
Thorax, December 1, 2005; 60(12): 998 - 1002.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
M. L. Drumm, M. W. Konstan, M. D. Schluchter, A. Handler, R. Pace, F. Zou, M. Zariwala, D. Fargo, A. Xu, J. M. Dunn, et al.
Genetic Modifiers of Lung Disease in Cystic Fibrosis
N. Engl. J. Med., October 6, 2005; 353(14): 1443 - 1453.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
C. K. Haston and T. J. Hudson
Finding Genetic Modifiers of Cystic Fibrosis
N. Engl. J. Med., October 6, 2005; 353(14): 1509 - 1511.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. P. Hersh, D. L. DeMeo, C. Lange, A. A. Litonjua, J. J. Reilly, D. Kwiatkowski, N. Laird, J. S. Sylvia, D. Sparrow, F. E. Speizer, et al.
Attempted Replication of Reported Chronic Obstructive Pulmonary Disease Candidate Gene Associations
Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 71 - 78.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. L. DeMeo, J. C. Celedon, C. Lange, J. J. Reilly, H. A. Chapman, J. S. Sylvia, F. E. Speizer, S. T. Weiss, and E. K. Silverman
Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., December 15, 2004; 170(12): 1294 - 1301.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
M Johnson
Which smokers will acquire COPD?
Thorax, November 1, 2004; 59(11): 965 - 965.
[Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.