Alpha‐1‐antitrypsin PI phenotypes S and Z in Europe: an analysis of the published surveys

Abstract

The objective of the present study was to review published surveys on allelic frequencies S and Z in European populations to evaluate the validity of the reported data. More than a hundred studies on the topic, published since 1965 until 2000, were retrieved by Medline, Index Medicus and bibliographic references consultation. The criteria for studies selection were: 1) sample size> or =250 individuals; 2) alpha-1-antitrypsin phenotype determination performed by means of crossed antigen-antibody or isoelectric focusing in polyacrylamide gels; 3) PI type determination performed without any previous screening procedure; 4) S and Z 95% confidence interval (CI) of the reported outcomes with a calculated coefficient of variation <42.3 for S and <95.8 for Z; 5) S and Z 95% CI of the reported outcomes comprised within 95% CI limits of comparative hypothetical surveys designed with the same sample size of the questioned surveys and the highest/lowest frequencies accepted for a specific area, according to the figures of isogen boundary maps. Seventy studies comply with the five established criteria for analysis. According to the data of the selected studies, a geographical distribution on S and Z gene frequencies in Europe is proposed.

A Retrospective Study and Gene Analysis of Canine Sterile Panniculitis

“…The fact that sterile panniculitis is diagnosed most commonly in dachshunds, as in previous reports and in the first part of this study, may suggest genetic factors play a role in development of canine sterile panniculitis. According to Smith et al, 16% of human patients with sterile panniculitis had α 1 AT deficiency [31], and several mutational phenotypes can result in sterile panniculitis despite a normal serum concentration [4,10]. In fact, there are over 90 genetically recognizable alleles in human, some of which include SNP, deletional, or insertional mutations resulting in enzyme deficiency or altered enzyme function [4,6,10,17].…”

“…According to Smith et al, 16% of human patients with sterile panniculitis had α 1 AT deficiency [31], and several mutational phenotypes can result in sterile panniculitis despite a normal serum concentration [4,10]. In fact, there are over 90 genetically recognizable alleles in human, some of which include SNP, deletional, or insertional mutations resulting in enzyme deficiency or altered enzyme function [4,6,10,17]. In the veterinary field, Hughes et al investigated the serum α 1 AT concentration in nine dogs with sterile panniculitis, but could not demonstrate the deficient concentration [12].…”

“…α 1 AT is known to be highly polymorphic in many species [8,21]. In humans, over 90 mutant alleles of the α 1 AT gene have genetically been identified so far, some of which can result in sterile panniculitis despite normal serum α 1 AT levels [4,10]. The most frequent mutations found at DNA level for Pi S and Pi Z alleles are 264 Glu →Val and 342 Glu→Lys, respectively.…”

Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies

“…3 Heterozygotes for the S allele of a 1 -antitrypsin (PI*MS) comprise up to 28% of Southern Europeans and although they have plasma a 1 -antitrypsin levels that are 80% of the M allele, the deficiency is not associated with any clinical sequeale. In contrast, the Z allele is most common in northwest Europe with frequencies declining from West to East and from North to South.…”

“…In contrast, the Z allele is most common in northwest Europe with frequencies declining from West to East and from North to South. 3 Approximately 4% of Northern Europeans are heterozygous for the Z allele (PI*MZ) with one in 1700 being homozygotes (PI*Z). The Z allele results in plasma levels that are 10 -15% of the M allele.…”