Analysis of the allelic diversity of a (CA)n repeat polymorphism among alpha 1-antitrypsin gene products from northern Portugal.

The level of molecular heterogeneity associated with alpha 1-antitrypsin gene products was assessed in the population of northern Portugal using three restriction fragment length polymorphisms (RFLPs) corresponding to specific amino acid substitutions and a highly variable (CA)n repeat polymorphism located at the 5' end of the PI gene. The allelic affinities inferred from the analysis of the DNA polymorphisms essentially agree with the evolutionary pattern proposed for the PI gene products on the basis of their amino acid sequences. PI*Z can be considered the most recent common PI allele and was found to be associated with the same predominant haplotype previously reported in northern European populations, thus confirming the hypothesis that most European Z alleles are derived from a single mutation. However, a rare deficient variant that is the likely result of a recurrent Z mutation on an M2 or M4 background was additionally observed. PIS was also found to be associated with a strongly predominant haplotype and seems to be the second most recent PI common allele, while M2 and M3 show weaker associations, suggesting more ancient origins of their corresponding mutations. M1Ala213 and M1Vat213 display more homogeneous (CA)n allele frequency distributions, M1Ala213 representing the most ancient PI allele as inferred from its highest variance in (CA)n allele length.