ABSTRACT
Our understanding of the inheritance of normal and abnormal alpha 1 -antitrypsin (alAT) genes began with the observation that emphysema and the absence of alpha 1-globulin were transmitted to more than one generation (1). The variant X was the first alAT variant of normal identified (2). The very rare X variant, characterized on agrose-gel electrophoresis as a slow migrating doublet, was not associated with the disease or a low alA T level. This observation, in combination with the already identified deficient and common normal variants, led Axelsson and Laurell (2) to propose that alAT was a three-allele system that was codominantly inherited. At about the same time, Fagerhol and Braend (3), utilizing the new technique of starch-gel electrophoresis to evaluate serum electrophoretic polymorphism, determined that variation in the prealbumin region was the result of electrophoretic variants of alAT. Together these variants constituted an allelic system that early investigators called the Pi (protease inhibitor) system. Variants, initially named according to their migration rates in a starch-gel electrophoresis system, were divided into three groups: medium (M), fast (F), and slow (S). The very slow (Z) variant was later added to the allelic system (4).
