α1-Antitrypsin (α1AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic protein associated with isoelectric focusing (IEF) patterns typical for each variant. α1AT V(munich), a previously unreported normal α1AT variant, has a unique IEF banding pattern in which the 7 and 8 α1AT protein bands focus with the normal M-type 7 and 8 bands, despite the fact that the major fraction of the V(munich) protein focuses in the 'V' region of the IEF gel. To characterize the molecular basis of this variant and its unique IEF pattern, DNA sequence analysis of the coding exons of the V(munich) α1AT gene was carried out using the polymerase chain reaction. The V(munich) allele differed from the common normal M1(Val213) α1AT allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change Asp2 GAT → Ala GCT. Inheritance of the allele was confirmed by family analysis using allele-specific amplification with the polymerase chain reaction. The Asp2 → Ala mutation explains the cathodal position of the V(munich) protein on IEF, as there is a substitution of a negatively charged amino acid by a neutral one. It is important that, in the context that the normal M-type α1AT 7 and 8 bands on IEF analysis are composed of α1AT molecules in which the first five residues have been cleaved, the tion of the V(munich) mutation within the first five amino acids accounts for the V(munich) 7 and 8 bands focusing with the normal M-type 7 and 8 bands, i.e., the α1AT proteins making up these bands do not contain the first five amino acids and thus cannot reflect the difference between V(munich) and the normal M1(Val213) α1AT protein.

Original languageEnglish
Pages (from-to)810-816
Number of pages7
JournalAmerican journal of human genetics
Issue number4
StatePublished - Apr 18 1990


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