Molecular mechanisms of alpha(1)-antitrypsin null alleles

초록

Alpha(1)-antitrypsin (alpha(1)-AT) is the most abundant circulating inhibitor of serine proteases and therefore is essential to normal protease-anti-protease homeostasis. Inheritance of two parental alpha(1)-AT deficiency alleles is associated with a substantially increased risk for development of emphysema and liver disease. In very rare circumstances individuals may inherit alpha(1)-AT null alleles. Null alpha(1)-AT alleles are characterized by the total absence of serum alpha(1)-AT. These alleles represent the extreme end in a continuum of alleles associated with alpha(1)-AT deficiency. The molecular mechanisms responsible for absence of serum alpha(1)-AT include splicing abnormalities, deletion of alpha(1)-AT coding exons and premature stop codons. While these alleles comprise only a small proportion of alpha(1)-AT alleles associated with profound alpha(1)-AT deficiency, studies of their molecular mechanisms provide valuable insights into the structure, gene expression and intracellular transport of alpha(1)-AT. (C) 2000 HARCOURT PUBLISHERS LTD.

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