Molecular biology and respiratory disease. 7. The alpha 1 antitrypsin gene and chronic lung disease.

The cxl antitrypsin gene and chroni-c lung disease N Kalsheker, K Morgan Alpha, antitrypsin or cx, proteinase inhibitor is the major serine proteinase inhibitor (serpin) present in the blood.An important physiological function of a, antitrypsin is thought to be protection of the lower respiratory tract from damage by neutrophil elas- tase.' Consequently, genetic deficiency of a, antitrypsin is associated with a 20-30 fold increased risk of developing progressive lung damage, particularly in individuals who smoke.2The mean plasma concentration is 1 4 g/l and the protein has a molecular weight of about 54 kilodaltons.The protease-antiprotease theory of emphysema predicts that an imbalance be- tween proteases, such as neutrophil elastase, and inhibitors, such as a, antitrypsin, has an important role in the pathogenesis of chronic lung disease, and this hypothesis has been tested extensively in an attempt to obtain a better understanding of the mechanisms resulting in chronic lung damage.34This article will focus on (1) the application of molecular biology techiques* to the study of the cx, antitrypsin gene; (2) the characterisa- tion of molecular variants of axl antitrypsin; and (3) the prospects for gene therapy.