Holgate Stephen T, Davies Donna E, Powell Rob M, Holloway John W
School of Medicine, University of Southampton, SO17 1BJ Southampton, UK.
Pulm Pharmacol Ther. 2006;19(1):3-11. doi: 10.1016/j.pupt.2005.02.008. Epub 2005 Jun 13.
Asthma is a complex disorder in which major genetic and environmental factors interact to both initiate the disease and modify its progression. While asthma is recognised as a disorder of the conducting airways characterised by Th2-directed inflammation, it is being increasingly apparent that alteration of the structural cells of the airways (airway remodelling) is also fundamental to disease chronicity and severity. The gene ADAM33, encoding a novel member of a identified as an asthma susceptibility gene as the result of a positional cloning effort in a cohort of families recruited form the UK and USA. Subsequent genetic studies have now provided evidence that ADAM33 may be involved in determining lung function throughout life, associated with early life lung function as well as increased decline therapeutic intervention in asthma and future work will focus on the mechanisms by which it alters lung function and bronchial hyperresponsiveness.
哮喘是一种复杂的疾病,主要的遗传和环境因素相互作用,引发疾病并影响其进展。虽然哮喘被认为是一种以Th2介导的炎症为特征的传导气道疾病,但越来越明显的是,气道结构细胞的改变(气道重塑)对于疾病的慢性化和严重程度也至关重要。基因ADAM33编码一种新的金属蛋白酶解聚素和金属蛋白酶家族成员,在一项从英国和美国招募的家庭队列中进行的定位克隆研究中,该基因被确定为哮喘易感基因。随后的遗传学研究现已提供证据表明,ADAM33可能参与决定一生的肺功能,与早期肺功能有关,也与哮喘中肺功能的加速下降有关。未来的工作将集中在其改变肺功能和支气管高反应性的机制上。