Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema

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 reg...

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Main Authors: V. I. Konenkov, V. V. Nimaev, A. V. Shevchenko, V. F. Prokofiev
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2024-07-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/4186
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author V. I. Konenkov
V. V. Nimaev
A. V. Shevchenko
V. F. Prokofiev
author_facet V. I. Konenkov
V. V. Nimaev
A. V. Shevchenko
V. F. Prokofiev
author_sort V. I. Konenkov
collection DOAJ
description 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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spelling doaj-art-803d4f19b9fb490988fe7167824ed0e92025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-07-0128443344210.18699/vjgb-24-491478Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedemaV. I. Konenkov0V. V. Nimaev1A. V. Shevchenko2V. F. Prokofiev3Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesCells 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.https://vavilov.elpub.ru/jour/article/view/4186primary lymphedemasecondary lymphedemavegfmmptimpkdrnrp.
spellingShingle V. I. Konenkov
V. V. Nimaev
A. V. Shevchenko
V. F. Prokofiev
Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
Вавиловский журнал генетики и селекции
primary lymphedema
secondary lymphedema
vegf
mmp
timp
kdr
nrp.
title Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
title_full Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
title_fullStr Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
title_full_unstemmed Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
title_short Polymorphism of angiogenesis regulation factor genes (<i>VEGF/VEGFR</i>), and extracellular matrix remodeling genes (<i>MMP/TIMP</i>), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
title_sort polymorphism of angiogenesis regulation factor genes i vegf vegfr i and extracellular matrix remodeling genes i mmp timp i and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema
topic primary lymphedema
secondary lymphedema
vegf
mmp
timp
kdr
nrp.
url https://vavilov.elpub.ru/jour/article/view/4186
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AT vvnimaev polymorphismofangiogenesisregulationfactorgenesivegfvegfriandextracellularmatrixremodelinggenesimmptimpiandthelevelsoftheirproductsinextracellulartissuesofpatientswithprimaryandsecondarylymphedema
AT avshevchenko polymorphismofangiogenesisregulationfactorgenesivegfvegfriandextracellularmatrixremodelinggenesimmptimpiandthelevelsoftheirproductsinextracellulartissuesofpatientswithprimaryandsecondarylymphedema
AT vfprokofiev polymorphismofangiogenesisregulationfactorgenesivegfvegfriandextracellularmatrixremodelinggenesimmptimpiandthelevelsoftheirproductsinextracellulartissuesofpatientswithprimaryandsecondarylymphedema