vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-49vavilov-4186Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSПолиморфизм генов факторов регуляции ангиогенеза (VEGF/VEGFR), генов ремоделирования внеклеточного матрикса (MMP/TIMP) и уровни соответствующих белков во внеклеточных тканях пациентов с первичной и вторичной лимфедемойPolymorphism of angiogenesis regulation factor genes (VEGF/VEGFR), and extracellular matrix remodeling genes (MMP/TIMP), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedemahttps://orcid.org/0000-0001-7385-6270КоненковВ. И.KonenkovV. I.

Новосибирск

Novosibirsk 

https://orcid.org/0000-0002-9889-3729НимаевВ. В.NimaevV. V.

Новосибирск

Novosibirsk 

https://orcid.org/0000-0001-5898-950XШевченкоА. В.ShevchenkoA. V.

Новосибирск

Novosibirsk 

shalla64@mail.ruhttps://orcid.org/0000-0001-7290-1631ПрокофьевВ. Ф.ProkofievV. F.

Новосибирск

Novosibirsk 

Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал Федерального исследовательского центра Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesRussian Federation202411072024284433442Copyright © Коненков В.И., Нимаев В.В., Шевченко А.В., Прокофьев В.Ф., 20242024Коненков В.И., Нимаев В.В., Шевченко А.В., Прокофьев В.Ф.Konenkov V.I., Nimaev V.V., Shevchenko A.V., Prokofiev V.F.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4186

Клетки различных органов и систем осуществляют свои функции и межклеточные взаимодействия не в инертной среде, а в микроокружении тканевых жидкостей. Нарушения нормального дренажа тканевых жидкостей сопровождают лимфедему. Важный механизм регуляции ангиогенеза и васкулогенеза в подкожной клетчатке – выработка и рецепция факторов роста эндотелия сосудов в сочетании с регуляцией матриксных металлопротеиназ. Цель настоящего исследования: сравнительный анализ полиморфизма генов фактора роста эндотелия сосудов и его рецепторов вместе с генами матриксных металлопротеиназ при двух формах лимфедемы, анализ взаимосвязи полиморфизма этих генов с уровнем фактора роста эндотелия сосудов и матриксных металлопротеиназ и их ингибиторов в сыворотке крови и пораженных тканях. Полиморфизм VEGF (rs699947, rs3025039), рецепторов к нему KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), матриксных металлопротеиназ MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), ингибитора металлопротеиназ Timp1 (rs6609533) и их комбинаций проанализирован методами анализа длин рестрикционных фрагментов и TaqMan RT­PCR. Уровень белков в сыворотке и тканевой жидкости определяли с использованием тест­систем ELISA. Показаны изменения частот распределения генотипов ММР2 при первичной и ММР3 при вторичной лимфедеме. Высокодостоверные различия частот генотипов NRP2 обнаружены при сравнении первичной и вторичной лимфедемы. Выявлены особенности распределения «комплексных» генотипов при первичной и вторичной лимфедеме. Корреляционный анализ показал взаимозависимость концентрации исследуемых белковых продуктов MMP, TIMP и VEGF и выраженные различия в структуре корреляционных матриц пациентов с обеими формами лимфедемы. Продемонстрировано, что при первичной лимфедеме выявляются генотипы, ассоциированные с низкими значениями MMP2 и TIMP2 в сыворотке крови и тканевой жидкости, а при вторичной лимфедеме – иные связи концентраций исследуемых белков с комбинированными генетическими признаками

Cells of various organs and systems perform their functions and intercellular interactions not in an inert environment, but in the microenvironment of tissue fluids. Violations of the normal drainage of tissue fluids accompany lymphedema. An important mechanism of angiogenesis and vasculogenesis regulation in tissue fluids is the production and reception of vascular endothelial growth factors in combination with the regulation of matrix metalloproteinases. The aim of the work was to perform: a comparative analysis of some polymorphisms of vascular endothelial growth factor and their receptors and the genes encoding matrix metalloproteinases in two forms of lymphedema; an analysis of the relationship of these genes’ polymorphisms with the levels of vascular endothelial growth factor and matrix metalloproteinases and their inhibitors in serum and affected tissues. Polymorphism of VEGF (rs699947, rs3025039), KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), matrix metalloproteinases MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), Timp1 (rs6609533) and their combinations were analyzed by the Restriction Fragment Length Polymorphism method and TaqMan RT­PCR. The serum and tissue fluid levels were determined using the ELISA test system. Changes in the frequency distribution of MMP2 genotypes in primary and MMP3 in secondary lymphedema are shown. Significant frequency differences in NRP2 genotypes were revealed by comparing primary and secondary lymphedema. Features of the distribution of complex genotypes in primary and secondary lymphedema were revealed. The correlation analysis revealed the interdependence of the concentrations of the MMP, TIMP and VEGF products and differences in the structure of the correlation matrices of patients with both forms of lymphedema. It was shown that, in primary lymphedema, genotypes associated with low MMP2 and TIMP2 in serum and tissue fluid are detected, while in secondary lymphedema, other associations of the production levels with combined genetic traits are observed.

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The authors declare that there are no conflicts of interest present.