Effects of the protease inhibitor (Pi) polymorphism on alpha-1-antitrypsin concentration and elastase inhibitory capacity in human serum

Abstract

The concentration of .alpha.-1-antitrypsin (AAT) and its elastase inhibitory capacity (EIC) were investigated in vitro in sera from 1688 healthy Canberra [Australia] blood donors typed for electrophoretic variants of the protease inhibitor (Pi) locus. Nine Pl alleles were recorded in the sample, of which M1 was found at a frequency of nearly 70% and the other 8 were each at frequencies below 15%. As a class, heterozygotes among the 3 Pi M subtype alleles, M1, M2 and M3, have higher means and lower variances for AAT and EIC than do the three M subtype homozygotes. Among the 3 homozygotes M1M1 has highest AAT and EIC and among the heterozygotes dominance in M1M2 and M1M3 is towards or beyond the high M1M1 values. Of the 6 other Pi alleles recorded, 2 (F and G) have similar values to the M subtypes but the other 4 (I, N, S and Z) have lower values. The patterns of means and variances in AAT and EIC for the different M subtype genotypes do not support the precise threshold function postulated by Martin et Oakeshott (1983) to relate activity to Darwinian fitness. Several aspects of the results are consistent with a general positive relationship between activity and fitness.