The gene for AAT is on chromosome 14. There are over 100 known mutations. The normal allele is designated PiM, and the two most common abnormal alleles are designated PiS and PiZ. Heterozygotes PiMS and PiMZ may on occasion develop pulmonary and/or liver disease, but less often severe. The homozygotes PiSS and PiZZ, and the heterozygote PiSZ, are more likely to develop significant COPD and/or liver disease. The persons most likely to develop severe AAT deficiency and its complications have PiZZ. About 1 in 10 persons of European ancestry has one of the 5 abnormal phenotypes (the normal is PiMM). |