Origins and spreads of Alpha 1 antitrypsin variants in world human populations: a synthetic review

Abstract

Human Alpha 1 antitrypsin (AAT) or protease inhibitor (PI) is a highly polymorphic glycoprotein. In this review report distributions of all detected AAT allelic variants in different world populations are collected showing their anthropological usefulness. Some variants are related to AAT deficiency (AATD) which is one of the most common genetic disorders worldwide. Data on PIS and PIZ, most common AATD mutations, and their worldwide distribution are also reported. Studies on DNA haplotypes were particularly useful for the estimations of PIS and PIZ mutations ages and worldwide spread. According to these data, it seems very likely that the PIZ mutation occurred in Sweden and was spread into the rest of the European continent via the Baltic countries. However, in a second hypothesis authors suggested multiple origins of this mutation. The highest frequencies of the PIS mutation in the Iberian Peninsula were linked to an early occurrence of the mutation in this region, before its spread throughout the Europeans countries and the Iberian Peninsula settlements and trading networks. However, the PIS allele may have been further dispersed by multiple occurrences of the mutation. This multiple origins of AAT variants could explain the higher frequencies and haplotype diversities in PIM1Val and PIM2 alleles, rather than their older base alleles (PIM1Ala and PIM3, respectively). Data on rare variants, which seem not to be so rare in some populations, are still lacking. The only reliable data, on the age of a rare AATD variant, was given on an autochthonous allele (NullOurém).

Key words: Alpha 1 antitrypsin, allelic variants, worldwide distribution, origins and spread of mutations.