We demonstrate the cumulative effects of multiple SERPINA1 variants on α1-antitrypsin deficiency, lung function, and emphysema, thus, significantly increasing the frequency of SERPINA1 variation associated with respiratory disease in at-risk smokers.
As a monogenic disease, AATD appears to be an attractive target for gene therapy, particularly for patients with pulmonary dysfunction, where augmentation of functional AAT levels in plasma might slow down respiratory disease development.