Genotyping of alpha-1-antitrypsin in family studies

The aims of the study were to determine  -antitrypsin (AAT) genotype by a simple DNA-based method and to investigate the association of AAT genotype and serum AAT concentration in a group of ten families. AAT genotype was determined by PCR-RFLP and serum concentration by radial immunodiffusion in samples from each member of ten families (mother, father and child/children). In the group of parents, five normal genotypes, Pi MM, with a normal serum AAT concentration, and fifteen Pi MZ genotypes, four of them with slightly decreased (43%-66% of the mean) AAT concentration were detected. In the group of children, particular genotypes followed the mode of inheritance. There were eight Pi MZ, three of them with slightly decreased (52%-60% of the mean) AAT concentration, and five Pi ZZ genotypes with considerably decreased (24%-45% of the mean) AAT concentration. PCR-RFLP is the method of choice for AAT genotyping. AAT concentration is not a reliable biochemical marker of AAT deficiency. Determination of AAT genotype in family studies allows the risk of deficient allele inheritance to be followed-up and assessed. Early diagnosis of a deficient AAT genotype contributes to the success of currently widely available AAT replacement therapy.