Zhigaltsova-Kuchinskaya O.A.*, Sivitskaya L.N.**, Danilenko N.G.**, Zhigaltsov A.M.***, Nagornov I.V.****, Metelsky S.M.****
Alpha-1-antitrypsin deficiency: genetic fundamentals, epidemiology, role in the development of bronchopulmonary pathology
*State Educational Establishment «Belarusian Medical Academy of Post-Graduate Education», Minsk, Republic of Belarus
**State Scientific Establishment «Institute of Genetics and Cytology of Belarusian National Academy of Sciences», Minsk, Republic of Belarus
***Educational Establishment «Grodno State Medical University», Grodno, Republic of Belarus
****State Establishment «432 Order of the Red Star Main Military Clinical Center of the Armed Forces of the Republic of Belarus», Minsk, Republic of Belarus
Vestnik VGMU. 2015;14(6):39-52.
Abstract.
The article is dedicated to one of the serine proteases inhibitors – alpha-1-antitrypsin. Alpha-1-antitrypsin deficiency is a hereditary disease caused by the diminished level of blood serum alpha-1-antitrypsin occurring as a result of different mutations in PI (Proteinase inhibitor) gene and manifesting itself as chronic nonspecific lung diseases with the development of emphysema, the damage of the liver, vessels and other organs. Alpha-1-antitrypsin deficiency is very rarely recognized in the respiratory system diseases for various reasons. Hereditary predisposition is an important internal risk factor for the chronic respiratory diseases development. In patients with alpha-1-antitrypsin deficiency cough, shortness of breath, wheezing may be revealed. These symptoms are the reason for the diagnosis of bronchial asthma or chronic obstructive pulmonary disease. Bronchial asthma is the most common preliminary diagnosis, made in individuals with the reduced levels of alpha-1-antitrypsin, preceding the detection of alpha-1-antitrypsin deficiency. At the same time, an important role in the development of bronchial asthma is also assigned to alpha-1-antitrypsin deficiency. Bronchial asthma may occur as an independent disease, but can also develop against the background of hereditary deficiency of alpha-1-antitrypsin. In this article the attention is paid to the role of alpha-1-antitrypsin in the human body, the main mechanisms of alpha-1-antitrypsin action, conditions caused by low levels of alpha-1-antitrypsin on different PI gene mutations.
This genetic disorder is common in European countries. The prevalence of PI gene allelic variants in Belarus has not been studied yet, screening aimed at the detection of deficient PI gene alleles carriage hasn’t been set going. According to the calculated data about 1 900 – 6 300 of patients with alpha-1-antitrypsin deficiency can be expected in Belarus. With these data taken into account replacement therapy appears to be extremely expensive. Timely identification of pathological PI gene alleles carriage allows to carry out measures aimed at the prevention of the development of the disease as well as manifest forms of pathology. In the absence of adequate therapy, the prognosis is unfavourable.
Key words: alpha-1-antitrypsin deficiency, chronic lung diseases, Proteinase inhibitor gene mutations.
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