Comparison of the properties of rare variants of alpha1-proteinase inhibitor expressed in COS-1 cells and assessment of their potential as risk factors in human disease.

Among the more than 75 known variants of alpha(1)-proteinase inhibitor, a sub-population of rare, point mutations causing single amino acid replacements have been identified and classified as "at risk" alleles for development of pulmonary disease. In most cases, it is not clear how the amino acid replacements typical of these variants change the properties of the inhibitor to increase risk of disease in the affected individuals. To begin to address this question, we mutagenized a wild type alpha(1)-proteinase inhibitor cDNA to encode a panel of eight different point mutants reported to be associated with increased risk for development of pulmonary disease.