Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Inheritance and Genetic Polymorphism

Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Inheritance and Genetic PolymorphismI suggested that inheritance in o^AT deficiency was recessive. Seen in retrospect this was not quite correct. It is now known that heterozygotes express the products of both normal and abnormal alleles. Today it is quite clear that alleles in the Pi-system are inherited in a codominant autosomal manner which means that all alleles express themselves irrespective of combination. The complex genetic polymorphism of the Pi-system was elucidated in 1967 by Fagerhol and Laurell.8 However, findings suggesting such polymorphism were made already in 1962. It may be of historic interest to mention one observation on the double arband which we published in 1963. This was the first description of PiFM.

Frequency of aXAT Deficiency in the Population
One of the characteristic features of axAT deficiency is the absence of a visible o^-band in a paper or agar gel electrophoresis. It was evident that a mere visual inspection of a strip was enough for diagnosis. At that time, health screening programs had become popular in Sweden. In 1962, the Swedish Board of Health arranged a mass screening of 100,000 people for asymptomatic disease. A chemical test battery was used and a subsample of7,000 adult sera was analyzed by paper electrophoresis. This subsample represented 70 percent of the unselected adult population studied. My colleague, Dr. Uno Axelsson, and his coworkers used this series to trace all cases with monoclonal gammopathies. I had the opportunity to screen the unique material for o^AT deficiency. By visual inspection, four sera were found to be deficient and the diagnosis was confirmed by analyses of trypsin inhibitory capacity. Using this representative population sample of adults, I could calculate the frequency of the gene causing oijAT deficiency. The frequency of homozygotes was one in 1,750. On the assumption of random mating in the province studied, Hardy-Weinbergs law could be applied and the gene frequency calculated to q = 0.024. This meant that the heterozygote frequency in the population was 0.047 or close to 5 percent. This simple visual inspection of 7,000 electrophoretic strips turned out to give an unexpectedly correct figure of the true gene frequency in the Scandinavian population.

Category: Health

Tags: emphysema, lung disease, trypsin inhibitory capacity