HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Holgate, S. T. Articles by Holloway, J. W. Search for Related Content PubMed PubMed Citation Articles by Holgate, S. T. Articles by Holloway, J. W.

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

¹ Allergy and Inflammation Research, Division of Infection, Inflammation and Repair, ² IIR Division and ³ Division of Human Genetics, School of Medicine, Southampton General Hospital, Southampton, UK.

CORRESPONDENCE: S. T. Holgate, Allergy and Inflammation Research, MP810, Level D, Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK. Fax: 44 2380 796960. E-mail: sth{at}soton.ac.uk

Keywords: Asthma, environment, genetics, inflammation, remodelling, risk factors

Received: July 3, 2006
Accepted October 25, 2006

While asthma is an inflammatory disorder of the airways usually associated with atopy, an important additional component is involvement of the epithelium and underlying mesenchyme acting as a trophic unit (EMTU).

In addition to allergens, a wide range of environmental factors interact with the EMTU, such as virus infections, environmental tobacco smoke and pollutants, to initiate tissue damage and aberrant repair responses that are translated into remodelling of the airways. While candidate gene association studies have revealed polymorphic variants that influence asthmatic inflammation, positional cloning of previously unknown genes is identifying a high proportion of novel genes in the EMTU.

Dipeptidyl peptidase (DPP) 10 and disintegrin and metalloproteinase (ADAM)33 are newly identified genes strongly associated with asthma that are preferentially expressed in the airway epithelium and underlying mesenchyme, respectively.

Also of increasing importance is the recognition that genes associated with asthma and atopy have important interactions with the environment through epigenetic mechanisms that influence their expression. This type of research will not only identify biomarkers of different types of asthma across the full range of phenotypic expression, but will also identify novel therapeutic targets that could influence the natural history of the heterogenes lung disease.

This article has been cited by other articles:

				S. T. Holgate, G. Roberts, H. S. Arshad, P. H. Howarth, and D. E. Davies The Role of the Airway Epithelium and its Interaction with Environmental Factors in Asthma Pathogenesis Proceedings of the ATS, December 15, 2009; 6(8): 655 - 659. [Abstract] [Full Text] [PDF]

				B. G. J. Dekkers, H. Maarsingh, H. Meurs, and R. Gosens Airway Structural Components Drive Airway Smooth Muscle Remodeling in Asthma Proceedings of the ATS, December 15, 2009; 6(8): 683 - 692. [Abstract] [Full Text] [PDF]

				M. Harada, K. Obara, T. Hirota, T. Yoshimoto, Y. Hitomi, M. Sakashita, S. Doi, A. Miyatake, K. Fujita, T. Enomoto, et al. A Functional Polymorphism in IL-18 Is Associated with Severity of Bronchial Asthma Am. J. Respir. Crit. Care Med., December 1, 2009; 180(11): 1048 - 1055. [Abstract] [Full Text] [PDF]

				G. H. Koppelman, D. A. Meyers, T. D. Howard, S. L. Zheng, G. A. Hawkins, E. J. Ampleford, J. Xu, H. Koning, M. Bruinenberg, I. M. Nolte, et al. Identification of PCDH1 as a Novel Susceptibility Gene for Bronchial Hyperresponsiveness Am. J. Respir. Crit. Care Med., November 15, 2009; 180(10): 929 - 935. [Abstract] [Full Text] [PDF]

				S. Saglani, S. A. Mathie, L. G. Gregory, M. J. Bell, A. Bush, and C. M. Lloyd Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite-Exposed Neonatal Mice Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 281 - 289. [Abstract] [Full Text] [PDF]

				N. Bedke, H. M. Haitchi, M. Xatzipsalti, S. T. Holgate, and D. E. Davies Contribution of Bronchial Fibroblasts to the Antiviral Response in Asthma J. Immunol., March 15, 2009; 182(6): 3660 - 3667. [Abstract] [Full Text] [PDF]

				P. Bogaert, K. G. Tournoy, T. Naessens, and J. Grooten Where Asthma and Hypersensitivity Pneumonitis Meet and Differ: Noneosinophilic Severe Asthma Am. J. Pathol., January 1, 2009; 174(1): 3 - 13. [Abstract] [Full Text] [PDF]

				E. Bouzigon, E. Corda, H. Aschard, M.-H. Dizier, A. Boland, J. Bousquet, N. Chateigner, F. Gormand, J. Just, N. Le Moual, et al. Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma N. Engl. J. Med., November 6, 2008; 359(19): 1985 - 1994. [Abstract] [Full Text] [PDF]