Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Frequency of aXAT Deficiency in the Population

Many years later Sveger, by screening 200,000 Swedish newborn children, found an almost identical homozygote frequency, namely one in 1,660. I wrote6 in 1965 that the gene frequency for a!AT deficiency was of such an order of magnitude that a restricted distribution of the gene seemed improbable. It is now known that the PiZ-gene probably is of Scandinavian origin and is evenly distributed there. The gene frequency in Scandinavia and northern Europe is higher than anywhere else in the world. In southern Europe and in the United States, the gene frequency is approximately half of that in Scandinavia; in Japan it is practically nil.
Early Support for the Proteolytic Theory: The Role of Granulocyte Elastase
Only a few years before the discovery of axAT deficiency there had been general agreement that emphysema should be defined in anatomic terms and that the destructive element was obligate (WHO, Report of an expert committee, 1961). Increased proteolytic activity might well be responsible for the loss of tissue substance but trypsin per se was not considered to be of any pathogenetic relevance. canadian neighbor pharmacy

It was just used as a tool for measurement of antiprotease activity in serum. Pioneer work from the US had demonstrated the most specific physiologic feature of emphysema to be reduced elastic recoil and increased compliance,11 but the elastin content of emphysematous lungs had been found to be normal by most investigators. Collagen was known to have little influence on lung compliance. Familial cases of emphysema had been published and a putative metabolic basis discussed, but there was no experimental support.
Unexpectedly and independent of our reports on axAT deficiency and emphysema, Gross et al13 published an important paper demonstrating the production of emphysema in rats after intratracheal administration of papain, a plant protease with broad spectrum proteolytic activity. Of course, these experiments supported the concept of a proteolytic mechanism behind human emphysema and a new era of experimental emphysema research had begun. An important observation connecting experimental and clinical medicine was made by Kueppers and Bearn when they demonstrated the ability of oijAT to inhibit proteolytic enzymes from human leukocytes.

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