Back to Search
Start Over
Evidence of a genetic contribution to lung function decline in asthma.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2011 Sep; Vol. 128 (3), pp. 479-84. Date of Electronic Publication: 2011 Jul 12. - Publication Year :
- 2011
-
Abstract
- There has been great progress in identifying new asthma susceptibility genes. In asthmatic subjects there is variable airway remodeling that includes features such as smooth muscle hypertrophy/hyperplasia, basement membrane thickening, and increased extracellular matrix deposition. Does airway remodeling have a genetic contribution in asthma? Data from different murine strains suggest there is a genetic contribution to the development and progression of airway remodeling. In human subjects it is important to consider what surrogate markers of remodeling have been used in genetic studies. Baseline FEV(1) and airway hyperresponsiveness are determined by a complex interplay of factors, including nonremodeling mechanisms; however, we consider a decline in FEV(1) as a robust marker of remodeling. To date, single nucleotide polymorphisms spanning ADAM33, ESR1, PLAUR, and VEGF have been associated with an excess decline in lung function in asthmatic subjects carrying the rare alleles (FEV(1), -13.0 to 55.2 mL/y excess). Interestingly these genes have overlapping functions in proteolytic pathways in the airways. There is accumulating evidence that genetic factors are important in the development of airway remodeling in asthmatic subjects, and further longitudinal studies with additional remodeling phenotypes and genome-wide association studies will identify novel susceptibility genes, leading to new approaches to target remodeling in asthmatic subjects.<br /> (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
- Subjects :
- ADAM Proteins genetics
Animals
Humans
Mice
Polymorphism, Single Nucleotide
Respiratory Function Tests
Respiratory System metabolism
Respiratory System physiopathology
Vascular Endothelial Growth Factor A genetics
Airway Remodeling genetics
Asthma genetics
Asthma physiopathology
Genetic Predisposition to Disease
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 128
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21752436
- Full Text :
- https://doi.org/10.1016/j.jaci.2011.05.036