Medical Genetics - V. M. Zaporozhan 2005

Multifactorial Diseases
Ecogenetics
Examples of ecogenetic pathological reactions — α1-antitrypsin deficiency

A classic example of an ecogenetic reaction is the response to atmospheric air pollution in $\alpha_1$-antitrypsin deficiency, which is a proteinase inhibitor. Even with minor damage to lung tissue caused by smoking and inhaling dusty air, Proteolytic Enzymes begin to destroy the affected areas. Normally, the Synthesis of the proteinase inhibitor is immediately triggered, which neutralizes the action of proteolytic enzymes and halts the destruction of lung tissue. In the case of a mutant genotype, proteinase inhibitors are not synthesized, and proteolytic enzymes completely destroy the damaged areas, leading to pulmonary emphysema.

The antitrypsin Gene family locus (14q32.1) is represented by the a₁-antitrypsin and a₁-antichymotrypsin (AAT) genes. Currently, over 100 gene allelic variants of AAT are known. The genetic Variants of the protein differ in their antitrypsin activity, electrophoretic mobility, and, as a rule, are functionally less active (M, S, Z alleles). Protein inactivity ("null allele") is most commonly caused by the recessive Z allele. In the European population, the frequency of homozygotes for this allele is 0.05%, and for heterozygotes, it is 4.5%. Recessive homozygotes for this allele are prone to developing chronic inflammatory processes and pulmonary emphysema (30 times more frequently than the population average). Heterozygotes are practically healthy; however, under conditions of high ambient air pollution, they rapidly develop chronic bronchopulmonary and occupational diseases. Analysis of the antitrypsin system is recommended for patients with chronic obstructive pulmonary disease, emphysema, and Bronchial Asthma, as well as during occupational health screenings and hiring selections for relevant industries.