Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma

Background: Asthma is a genetically complex disease characterized by respiratory symptoms, intermittent airway obstruction and airway hyper-responsiveness due to airway inflammation and remodelling. The ADAM33 gene is associated with asthma and airway hyper-responsiveness and is postulated as a gene for airway remodelling. Objective: To investigate whether polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in patients with asthma. Methods: In a cohort of 200 asthma patients followed over 20 years, eight single nucleotide polymorphisms of the ADAM33 gene were analysed to estimate their effect on annual FEV₁ decline. Results: The rare allele of the S_2 polymorphism was significantly associated with excess decline in FEV₁ (P < 0.05). Conclusion: These findings suggest that a variant in ADAM33 is not only important in the development of asthma but also in disease progression, possibly related to enhanced airway remodelling.