genetics

Last reviewed 11/2023

The condition is autosomal co-dominant and the gene is located on chromosome 14.

Alpha-1-antitrypsin is part of a family of protease inhibitors whose genetic variants are classified on the basis of their electrophoretic mobility - M for normal, S for slow, and Z for very slow.

The normal genotype is pi-MM; pi-SS homozygotes have 50% of normal alpha1-antitrypsin activity; pi-ZZ homozygotes, only 10%. S and Z variants both result from a single amino-acid substitution.

In many forms of alpha-1-antitrypsin deficiency, the protein is synthesised normally but it accumulates within the hepatocyte. The exception is pi-null in which no alpha1-antitrypsin is produced.