Alpha 1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z.
alpha 1-Antitrypsin (AT) is the principal serum inhibitor of proteolytic enzymes such as neutrophil elastase. AT can exist as over 90 different genetically determined variants known as the Pi system; the three most important variants are type M (90% of population) and types S and Z, two of the commoner abnormal variants. Homozygotes of type Z have a severe reduction in the serum AT concentration and may develop pulmonary emphysema or hepatic cirrhosis. Heterozygotes of type SZ have a less severe reduction in serum AT concentration and the association with clinical disease is less clear. The S and Z variants are found mainly among those of European stock. The gene frequency for Pi type Z is highest on the north-western seaboard of the continent and the mutation seems likely to have arisen in southern Scandinavia. The distribution of type S is quite different; the gene frequency is highest in the Iberian peninsula and the mutation is likely to have arisen in that region. A population survey for determining the number of type Z homozygotes in a given community is important for planning purposes now that AT replacement therapy is potentially available.
Hutchison
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DC
Department of Respiratory Medicine, King's College School of Medicine, London, U.K.
D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D010641:Phenotype; D015995:Prevalence; D019896:alpha 1-Antitrypsin Deficiency / Q000453:epidemiology* / Q000235:genetics