Stepanova Ye. I., Kolpakov Ye., Zyhalo V. M., Lytvynets O. M., Kondrashova V. H., Vdovenko V. Yu., Skvars’ka O. O., Leonovych O. S.
Influence of eNOS gene 4a/b VNTR polymorphism on development of endothelial dysfunction and respiratory system disorders in children – residents of radioactively contaminated areas
Objective is to study the role of åNOS gene polymorphism in the development of endothelial dysfunction and functional disorders of the respiratory system in children – residents of radioactively contaminated areas.
Materials and methods. Total of 184 children were examined to determine the possible associative links between åNOS gene intron 4m polymorphism and indices characterizing the functional state of the endothelium and the bronchopulmonary system. Of them the main group of children consisted of 135 children-residents of radioactively contaminated areas, the control group – of 49 healthy children who lived in “clean” regions by the radioactive contamination and were not belonging to victims of the Chernobyl accident contingents. The molecular genetic study determining the åNOS gene intron 4 polymorphism was performed. An examination of lung ventilation capacity was evaluated using the pneumotachography method. The thermographic method was used for registering the endothelium dependent reaction of the vascular bed to changes in blood supply conditions. The levels of nitrogen compounds (NO2- and NO3-) were determined by the standard method using Hriss reagent. The level of body incorporated 137Cs was determined using human radiation counter Skrynner 3M (Institute of Human Ecology).
Results. Children of the main group did not differ from that of control and literature data by the frequency of genotypes 4a/b and åNOS gene allele polymorphism. An increase in the duration of circulation restoration up to the initial level after occlusion test was noted in children of the main group with genotype 4a/4b comparing to children with genotype 4b/4b; a decrease in the nitrite content was observed in blood serum. The integral indices of elasticity and tensility of the lung tissue, respiratory permeability were decreased; the signs of bronchospasm were recorded 1.5 times more often. These adverse effects were associated with the presence of genotype allele 4a, the signs of endothelial dysfunction and the level of the incorporated 137Cs.
Conclusions. More pronounced changes in vascular endothelial reaction to occlusion and the significant decrease of serum nitrite level in allele 4a carriers, especially in children who live in adverse ecological conditions, give the right to include them into the risk group for the development of endothelial dysfunction, and to conside pulmonary dysfunction as one of its manifestations.
Key words: children, the Chernobyl disaster, radioactively contaminated areas, åNOS gene polymorphism, endothelial dysfunction, nitric oxide, the respiratory system.
Problems of radiation medicine and radiobiology. 2015;20:432-444.
|