alpha
1 antitrypsin deficiency

The best documented genetic risk factor for COPD is

1 antitrypsin deficiency. However, this is rare and is present in
only 1-2% of patients with COPD.
1 antitrypsin is a
glycoprotein responsible for most of the antiprotease activity in
serum. Its gene is highly polymorphic, but some genotypes
(usually ZZ) are associated with low serum concentrations
(typically 10-20% of normal). Severe deficiency of
1 antitrypsin
is associated with premature and accelerated development of
COPD in smokers and non-smokers, though the rate of decline
in lung function is greatly accelerated in those who smoke.
The
1 antitrypsin status of patients with severe COPD who
are less than 40 years old should be determined since over half
of such patients have this deficiency. Detection of such cases
identifies family members who will require genetic counselling
and patients who might be suitable for future potential
treatment with
1 antitrypsin replacement.