Alpha-1-antitrypsin (AAT) is an acute phase protein secreted in the circulation after production in the liver.
AAT is the main inhibitor of serine proteases, thereby protecting various organs against inflammation-induced tissue damage.
It is well known that gene variants dictate the plasma AAT concentration according to a co-dominant model, the most common variant associated with AAT plasma deficiency is the Z (rs28929474) variant.
The genotype ZZ alpha-1-antitrypsin is a monogenic autosomal recessive disorder generating a strong pressure to develop pulmonary emphysema or liver cirrhosis.
In a EU database, about 5000 subjects are registered.
However, the Z-allele has a population gene frequency of 1 : 3000 to 1 : 5000, depending on the geographic descent of the population from Scandinavia.
Thus, a far higher number of unaffected individuals must exist than the number of subjects known with disease expression of either pulmonary emphysema or liver cirrhosis or rarely both.
This suggests that a balance of currently unknown signalling pathways is important to stay healthy or obtain disease.
Due to the genetic and environmental diversity of Alpha1-Deficiency subjects, identification of critical elements related to a lung or liver disease process from cross-sectional studies requires large cohorts.
This is why clinical scientists with an interest in alpha-1-antitrypsin joined to form the Alpha1 International Registry, AIR.
This website has national flags of all members of AIR.
If you hit the flag of your country, you will be directed to information about this condition in your own language and will see contact details to obtain more specific information.