Genetic mechanisms of primary lung emphysema

Abstract

A personalized approach to the treatment of a polygenic disease, such as pulmonary emphysema, provides unique opportunities for selection of effective treatment in each clinical case. Progress of understanding molecular mechanisms behind emphysema allows to take a new look at classification, causes of phenotype variability, prognosis and preventive measures before clinical manifestation.The aim of this review was to bring together the available data of genetic mutations impact to lung emphysema, its endotypes characteristics, and determine the personalized treatment approaches.Results. The attention of clinicians in the diagnosis of essential emphysema is focused on measurement the level of α1-antitrypsin in serum and mutations of SERPINA1 gene in exons 3, 4, 5 and 6. This is important, though not complete information about the causes and disease prognosis. This routine approach do not take into account the influence of genes-modifiers and gene-gene interactions. At the same time, intact SERPINA1 does not guarantee a zero risk of primary emphysema. To date, a wide range of genetic defects has been identified. These defects are capable, to a varying degree, to cause the disease, determine its clinical manifestations, severity and frequency of exacerbations.Conclusion. Wholeexome sequencing with the identification of affected metabolic pathways makes it possible to see a complete molecular portrait of emphysema, determine the endotype and select targeted therapy for each clinical case.