This differential expression of the PI gene might elucidate the puzzling heterozygote controversy in which heterozygotes have been found to be affected with AAT deficiency.
In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency.
In recent studies, a protease-to-protease inhibitor imbalance in patients with alpha 1-antitrypsin deficiency was thought to be a mechanism contributing to the development of chronic pancreatitis.