Alpha-1 Antitrypsin Genotype Distribution in Patients with Emphysema

Alpha-1 antitrypsin deficiency (AATD) is a rare inherited condition characterized by low serum levels of alpha-1 antitrypsin (AAT). In this study, we aimed to determine the frequency of AATD in patients with emphysema, to show the distribution of AATD genotypes according to the type and localization of emphysema, and to evaluate patients in terms of augmentation therapy.

This cross-sectional descriptive study included 794 patients with emphysema on high-resolution thoracic tomography (HRCT) between December 2022 and December 2024 at the chest disease clinic of the Samsun Training and Research Hospital. During screening, demographic characteristics (age and sex), smoking status (smoker, ex-smoker, and non-smoker), types of emphysema (centriacinar emphysema, panacinar emphysema, and paraseptal emphysema), and location (upper, middle, and lower lobes) were recorded. Dried blood spot samples collected from the fingertips of patients with emphysema were screened for Alpha-1 Antitrypsin (AAT) genotype deficiency. AAT levels and PFT were evaluated in patients with AATD.

In the AAT genotyping results, no mutations were detected in 763 (96%) patients, while AATD mutations were detected in 31 (4%) patients. While AATD was more common in panacinar emphysema, no mutations were detected in paraseptal emphysema. The most common mutations were PI*M/M malton (n=9), PI*M/Z (n=7), PI*M/I (n=4), and PI*M malton/M malton (n=4). AAT level was found to be low in PI*Z/Z (n=3), PI*M malton/M malton (n=4) and PI*Z/M malton (n=1) genotypes (0.20±0.2 g/L). Six patients received augmentation therapy for AATD: three had PI*Z/Z, two had PI*M malton/M malton, and one had the PI*Z/M malton genotype.

As a result, analyzing AAT genotypes in patients with emphysema may provide an early diagnosis of AATD, allowing the application of preventive measures and augmentation therapy strategies.