Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema

Among the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, wh...

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Autores principales:	A. V. Shevchenko, V. F. Prokofyev, V. I. Konenkov, R. S. Khapaev, V. V. Nimaev
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	primary lymphedema matrix metalloproteinases genes vascular endothelial growth factor gene gene networks mathematical modelling Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/44499983f6194137b4996746460fb067
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spelling	oai:doaj.org-article:44499983f6194137b4996746460fb0672021-11-18T08:03:49ZPolymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema1563-06252313-741X10.15789/1563-0625-POV-1913https://doaj.org/article/44499983f6194137b4996746460fb0672020-05-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1913https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XAmong the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, which are responsible for lympho- and vasculogenesis. Moreover, matrix metalloproteinases (ММР) may act as regulators of both lymphangiogenesis, and angiogenesis. Since the regulatory regions of VEGFA gene, as well as of ММР genes are polymorphic, one may suggest, that their different expression level, determined by these polymorphisms, could be associated with development of swellings typical for lymphedema.We have analyzed gene polymorphisms in two regulatory regions of vascular endothelial growth factor-A VEGF-A (rs 699947 and rs 3025039), and matrix metalloproteinase genes MMP2 (rs 2438650), MMP3 (rs 3025058), MMP9 (rs 3918242), and their combinations in the patients with primary lymphedema.A group of patients with primary lymphedema included 72 subjects (55 women and 17 men) at the age of 18 to 81 years. Control group included 526 inhabitants of Novosibirsk (153 men, 373 women) without chronic diseases, comparable for age with lymphedema patients. We have performed typing of regulatory regions in VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 genes (rs 3918242). Fifteen complex genotypes have been revealed that were positively associated with disease. Analysis of the gene network topology has outlined the main intergenic interactions upon primary lymphedema development. MMP2 -1306 CC, MMP9 -1562CC and VEGF +936CC arrange the basic knots in the gene network (53% of total interactions). A number of significantly different complex genotypes was revealed at patients with primary lymphedema with normal body mass index (BMI < 25) and obesity (BMI < 30). Hence, frequency of complex genotype VEGF +936 CC: MMP3 -1171 5А6А:MMP9 -1562 CC in the patients with obesity is increased more 5.5-fold compared to the patients with normal BMI.The data obtained may presume a certain value of the analyzed gene polymorphisms in pathogenesis of primary lymphedema. Topological analysis of gene networks allows to study the structural and functional organization of gene-gene interactions for development of approaches to individyal preventive maintenance and therapy of the disease.A. V. ShevchenkoV. F. ProkofyevV. I. KonenkovR. S. KhapaevV. V. NimaevSPb RAACIarticleprimary lymphedemamatrix metalloproteinases genesvascular endothelial growth factor genegene networksmathematical modellingImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 3, Pp 497-506 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	primary lymphedema matrix metalloproteinases genes vascular endothelial growth factor gene gene networks mathematical modelling Immunologic diseases. Allergy RC581-607
spellingShingle	primary lymphedema matrix metalloproteinases genes vascular endothelial growth factor gene gene networks mathematical modelling Immunologic diseases. Allergy RC581-607 A. V. Shevchenko V. F. Prokofyev V. I. Konenkov R. S. Khapaev V. V. Nimaev Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
description	Among the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, which are responsible for lympho- and vasculogenesis. Moreover, matrix metalloproteinases (ММР) may act as regulators of both lymphangiogenesis, and angiogenesis. Since the regulatory regions of VEGFA gene, as well as of ММР genes are polymorphic, one may suggest, that their different expression level, determined by these polymorphisms, could be associated with development of swellings typical for lymphedema.We have analyzed gene polymorphisms in two regulatory regions of vascular endothelial growth factor-A VEGF-A (rs 699947 and rs 3025039), and matrix metalloproteinase genes MMP2 (rs 2438650), MMP3 (rs 3025058), MMP9 (rs 3918242), and their combinations in the patients with primary lymphedema.A group of patients with primary lymphedema included 72 subjects (55 women and 17 men) at the age of 18 to 81 years. Control group included 526 inhabitants of Novosibirsk (153 men, 373 women) without chronic diseases, comparable for age with lymphedema patients. We have performed typing of regulatory regions in VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 genes (rs 3918242). Fifteen complex genotypes have been revealed that were positively associated with disease. Analysis of the gene network topology has outlined the main intergenic interactions upon primary lymphedema development. MMP2 -1306 CC, MMP9 -1562CC and VEGF +936CC arrange the basic knots in the gene network (53% of total interactions). A number of significantly different complex genotypes was revealed at patients with primary lymphedema with normal body mass index (BMI < 25) and obesity (BMI < 30). Hence, frequency of complex genotype VEGF +936 CC: MMP3 -1171 5А6А:MMP9 -1562 CC in the patients with obesity is increased more 5.5-fold compared to the patients with normal BMI.The data obtained may presume a certain value of the analyzed gene polymorphisms in pathogenesis of primary lymphedema. Topological analysis of gene networks allows to study the structural and functional organization of gene-gene interactions for development of approaches to individyal preventive maintenance and therapy of the disease.
format	article
author	A. V. Shevchenko V. F. Prokofyev V. I. Konenkov R. S. Khapaev V. V. Nimaev
author_facet	A. V. Shevchenko V. F. Prokofyev V. I. Konenkov R. S. Khapaev V. V. Nimaev
author_sort	A. V. Shevchenko
title	Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
title_short	Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
title_full	Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
title_fullStr	Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
title_full_unstemmed	Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema
title_sort	polymorphism of vascular endothelial growth factor gene (<i>vegf</i>) and matrix metalloproteinase (<i>ммр</i>) genes in primary limb lymphedema
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/44499983f6194137b4996746460fb067
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Polymorphism of vascular endothelial growth factor gene (<i>VEGF</i>) and matrix metalloproteinase (<i>ММР</i>) genes in primary limb lymphedema

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