SERPINA1 and pulmonary emphysema: The human Z allele is a deletion which results in an amino acid substitution changing the conformation of the AAT molecule, the ZZ genotype is responsible for 98% of AAT represents the most severe emphysema.103 Furthermore, in cultured AAT mutant epithelial cells, the ER stress and consequent release of inflammatory cytokines and chemokines are exacerbated by exposure to cigarette smoke, consistent with the enhanced disease in smokers.103