Objective is to study the role of еNOS gene polymorphism in the development of endothelial dysfunction and func tional 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 еNOS 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 con tamination and were not belonging to victims of the Chernobyl accident contingents. The molecular genetic study determining the еNOS 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 endothe lium dependent reaction of the vascular bed to changes in blood supply conditions. The levels of nitrogen com pounds (NO2 and NO3 ) were determined by the standard method using Hriss reagent. The level of body incorporat ed 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 geno types 4a/b and еNOS gene allele polymorphism. An increase in the duration of circulation restoration up to the ini tial 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 elastic ity and tensility of the lung tissue, respiratory permeability were decreased; the signs of bronchospasm were record ed 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.
Meta roboty – doslidyty rol' polimorfizmu geniv eNOS u rozvytku endotelial'noI dysfunktsiI ta funktsional' nykh rozladiv systemy dykhannia u ditey – meshkantsiv radioaktyvno zabrudnenykh terytoriy.Materialy i metody doslidzhennia. Dlia vyznachennia mozhlyvykh asotsiatyvnykh zv’iazkiv polimorfizmu u 4 mu introni gena eNOS z pokaznykamy, shcho kharakteryzuiut' funktsional'nyy stan endoteliiu ta bronkholegenevoI sys temy, provedeno obstezhennia 184 ditey. Z nykh osnovnu grupu sklaly 135 ditey – meshkantsiv radioaktyvno zabrud nenykh terytoriy, kontrol'nu – 49 ditey, iaki prozhyvaly v „chystykh ” shchodo radioaktyvnogo zabrudnennia regionakh i ne nalezhaly do postrazhdalykh vnaslidok Chornobyl's'koI avariI kontyngentiv. Provodyly molekuliarno gene tychne doslidzhennia z vyznachenniam polimorfizmu v 4 mu introni gena eNOS. Doslidzhennia ventyliatsiynoI spro mozhnosti legeniv otsiniuvaly za dopomogoiu metodu pnevmotakhografiI. Dlia reiestratsiI endoteliyzalezhnoI reaktsiI sudynnogo rusla na zminy umov krovopostachannia vykorystovuvaly termografichnyy sposib. Vyznachennia rivniv azotystykh spoluk NO2 ta NO3 provodyly za standartnoiu metodykoiu z vykorystanniam reaktyvu Grissa. Riven' inkorporovanogo 137Cs v organizmi vyznachaly za dopomogoiu lichyl'nyka vyprominiuvannia liudyny Skrynner 3M vyrobnytstva Instytutu ekologiI liudyny.Rezul'taty. Dity osnovnoI grupy za chastotoiu polimorfnykh 4a/b genotypiv ta aleliv 4a i 4b gena eNOS ne vidriznia lysia vid kontroliu ta danykh literatury. U ditey osnovnoI grupy z genotypom 4a/4b u porivnianni z dit'my, iaki ma ly genotyp 4b/4b, vidmichalosia zbil'shennia tryvalosti vidnovlennia krovoobigu do vykhidnogo rivnia pislia ok liuziynoI proby; sposterigalosia znyzhennia vmistu nitrytu v syrovattsi krovi; zmenshennia integral'nykh pokaznykiv elastychnosti i roztiazhnosti legenevoI tkanyny, prokhidnosti dykhal'nykh shliakhiv; u 1,5 raza chastishe reiestruvalysia oznaky bronkhospazmu. Tsi nespryiatlyvi efekty buly asotsiyovani z naiavnistiu u genotypi aleliu 4a, oznak endo telial'noI dysfunktsiI ta rivnem inkorporovanogo 137Cs.Vysnovky. Bil'sh vyrazni zminy endoteliyzalezhnoI reaktsiI sudyn na okliuziiu ta virogidne znyzhennia rivnia nitry tu v syrovattsi krovi u nosiIv aleliu 4a, osoblyvo u ditey, iaki prozhyvaiut' u nespryiatlyvykh ekologichnykh umovakh, nadaie pidstavy vidnesty Ikh do grupy ryzyku z rozvytku endotelial'noI dysfunktsiI, a porushennia funktsiI legeniv rozgliadaty iak odyn z II proiaviv.
Keywords: children; endothe lial dysfunction; nitric oxide; radioactively contaminated areas; the Chernobyl disaster; the respiratory system; еNOS gene polymorphism.
Ye. I. Stepanova, Ye. Kolpakov, V. M. Zyhalo, O. M. Lytvynets, V. H. Kondrashova, V. Yu. Vdovenko, O. O. Skvarska, O. S. Leonovych.