Transmission of the PiZ allele for alpha 1-antitrypsin deficiency: population genetic considerations.

It is shown that a simple preferential transmission of the PiZ allele by PiZ-heterozygous males for alpha 1-antitrypsin deficiency cannot maintain the observed polymorphism at the locus without invoking any viability or fertility selection against the PiZ gene carriers (heterozygotes or homozygotes). From the data on frequencies of PiZ alleles in Europe, the estimates of such selection coefficients are shown to be of the order of 5-20%, which seems too large for natural populations. Furthermore, an analysis of 26 nuclear families, each ascertained through a heterozygous PiZ or homozygous ZZ child, does not provide statistical evidence for such a hypothesis.