Evidence of a genetic contribution to lung function decline in asthma

Gerard H. Koppelman, Ian Sayers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)

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. (J Allergy Clin Immunol 2011;128:479-84.)

Original languageEnglish
Pages (from-to)479-484
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number3
DOIs
Publication statusPublished - Sep-2011

Keywords

  • Asthma
  • airway remodeling
  • genetic susceptibility
  • lung function decline
  • ENDOTHELIAL GROWTH-FACTOR
  • PLASMINOGEN-ACTIVATOR
  • AIRWAY RESPONSIVENESS
  • PLAUR POLYMORPHISMS
  • PULMONARY-FUNCTION
  • ALLERGIC DISEASE
  • CELL-MIGRATION
  • ADAM33 GENE
  • FOLLOW-UP
  • ASSOCIATION

Cite this