Nevertheless, in spite of these possible biasing facts, and taking into account all the aforementioned limitations, the present analysis has provided guiding estimation of the PI*S and PI*Z frequency values, and has clearly demonstrated that these two major AAT deficient alleles are in widespread distribution worldwide, and that there are substantial populations at risk for adverse health effects of AAT deficiency-related in many countries of the World. This evidence concerns the gene SERPINA1 and alpha 1-antitrypsin deficiency.