Detection of alpha-1 antitrypsin gene mutations by polymerase chain reaction in patients with chronic obstructive pulmonary disease

Introduction. The alpha-1 antitrypsin deficiency is the best described genetic cause of chronic obstructive pulmonary disease. The study of the alpha-1 antitrypsin deficiency, as the most important genetic risk factor for chronic obstructive pulmonary disease, is an important step in developing a strategy for the prevention and treatment of this disease. The aim of the study was detection of homozygous and heterozygous deficient gene alleles (protease inhibitor Z and protease inhibitor S) for alpha-1 antitrypsin in the group of patients with chronic obstructive pulmonary disease with the predominance of lung emphysema, as well as determination of a positive correlation between the serum levels of alpha-1 antitrypsin and the corresponding alpha-1 antitrypsin genotype. Material and Methods. The study included 90 patients, mutually unrelated individuals, hospitalized due to lung emphysema. The control group included 10 subjects, with no clinical signs of lung emphysema, but with a family history of chronic obstructive pulmonary disease. We attempted to identify the most common deficient alleles (protease inhibitor Z and protease inhibitor S) and the concentration of alpha-1 antitrypsin in the serum of the examinees. The polymorphism between the two allelic forms, protease inhibitor Z and protease inhibitor S, was detected by real-time polymerase chain reaction. Results. Protease inhibitor MM genotype alpha-1 antitrypsin was present in all 90 patients with the diagnosis of pulmonary emphysema, and the serum levels of alpha-1 antitrypsin were within the range of reference values. In the control group, there were two cases with mutated protease inhibitor MZ genotype, and in these 2 subjects the serum level of alpha-1 antitrypsin was at the lower limit of reference values. Conclusion. In patients diagnosed with lung emphysema, protease inhibitor MM genotype of alpha-1 antitrypsin and normal serum alpha-1 antitrypsin levels, the genetically- determined deficiency of alpha-1 antitrypsin is not responsible for the development of chronic obstructive pulmonary disease.