Evidence of a genetic contribution to lung function decline in asthma - 28/08/11
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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 FEV1 and airway hyperresponsiveness are determined by a complex interplay of factors, including nonremodeling mechanisms; however, we consider a decline in FEV1 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 (FEV1, −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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, airway remodeling, genetic susceptibility, lung function decline
Abbreviations used : ADAM33, AGER, AHR, ASM, ERK, ESR1, FVC, GWA, HHIP, LD, OVA, PAI, PAS, PLAUR, SNP, VEGF
Plan
Disclosure of potential conflict of interest: G. H. Koppelman has received research support from the Netherlands Asthma Foundation. I. Sayers has received research support from the Medical Research Council UK and Asthma UK. |
Vol 128 - N° 3
P. 479-484 - septembre 2011 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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