NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION

Age-related macular degeneration is one of the most widespread multifactorial eye diseases. Polymorphic functional alleles of vascular endothelial growth factor (VEGF) combined with matrix metalloproteinase (MMP) gene and tumor necrosis factor (TNF) gene variants may influence the development of dis...

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Autores principales: A. V. Shevchenko, V. F. Prokofyev, V. I. Konenkov, V. V. Chernykh, A. V. Eremina, L. V. Dudnikova, N. Yu. Kashkina, A. N. Trunov
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spelling oai:doaj.org-article:b700cda4be5342e9bbd6ea95a52fead32021-11-18T08:03:46ZNETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION1563-06252313-741X10.15789/1563-0625-2017-5-537-546https://doaj.org/article/b700cda4be5342e9bbd6ea95a52fead32017-10-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1353https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XAge-related macular degeneration is one of the most widespread multifactorial eye diseases. Polymorphic functional alleles of vascular endothelial growth factor (VEGF) combined with matrix metalloproteinase (MMP) gene and tumor necrosis factor (TNF) gene variants may influence the development of disease. We have performed frequency analysis of their polymorphisms in regulatory regions of VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 (rs 3918242), TNFα (rs1800630, rs1800629, rs 361525) genes, and their combinations in a group of patients with age-related macular degeneration (MD). Frequencies of TNFα (rs1800629) genotypes significantly differed for the MD patients and control group. Upon the combined genotype analysis, we have revealed six constellations of VEGF-ММР genes that were positively associated with the disease development. Five of them included minor homozygous genotype VEGF-2578АА. A combined analysis of VEGF – TNFα genes polymorphisms has shown presence of both positive and negative complex genotypes. The most significant differences have been detected by comparative analysis of the complex genotypes frequencies which included 8 polymorphic regulatory gene regions of all genes studied. In most genetic complexes associated with the disease development, homozygous TNFα-863СС, homozygous MMP2-1306 ТТ, and MMP9-1562СС genotypes have been detected, together with the combination of homozygous VEGFA+936СС genotype in the same patients. We can assume that harboring allelic variants, which may contribute to angiogenesis prorcesses is typical for the genome of patients with macular degeneration, along with low-level production of pro-inflammatory regulatory factors and enzymes participating in degradation of extracellular matrix. Analysis of complex genetic factors, procing some factors taking part at the pathological process being the regulators of production for each other, is more informative when detecting protective and resistant markers of the disease development rather than single genetic markers, thus being useful for genomic screening.A. V. ShevchenkoV. F. ProkofyevV. I. KonenkovV. V. ChernykhA. V. EreminaL. V. DudnikovaN. Yu. KashkinaA. N. TrunovSPb RAACIarticleage-related macular degenerationpolymorphism tnfvegf polymorphismммр polymorphismnetwork analysisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 19, Iss 5, Pp 537-546 (2017)
institution DOAJ
collection DOAJ
language RU
topic age-related macular degeneration
polymorphism tnf
vegf polymorphism
ммр polymorphism
network analysis
Immunologic diseases. Allergy
RC581-607
spellingShingle age-related macular degeneration
polymorphism tnf
vegf polymorphism
ммр polymorphism
network analysis
Immunologic diseases. Allergy
RC581-607
A. V. Shevchenko
V. F. Prokofyev
V. I. Konenkov
V. V. Chernykh
A. V. Eremina
L. V. Dudnikova
N. Yu. Kashkina
A. N. Trunov
NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
description Age-related macular degeneration is one of the most widespread multifactorial eye diseases. Polymorphic functional alleles of vascular endothelial growth factor (VEGF) combined with matrix metalloproteinase (MMP) gene and tumor necrosis factor (TNF) gene variants may influence the development of disease. We have performed frequency analysis of their polymorphisms in regulatory regions of VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 (rs 3918242), TNFα (rs1800630, rs1800629, rs 361525) genes, and their combinations in a group of patients with age-related macular degeneration (MD). Frequencies of TNFα (rs1800629) genotypes significantly differed for the MD patients and control group. Upon the combined genotype analysis, we have revealed six constellations of VEGF-ММР genes that were positively associated with the disease development. Five of them included minor homozygous genotype VEGF-2578АА. A combined analysis of VEGF – TNFα genes polymorphisms has shown presence of both positive and negative complex genotypes. The most significant differences have been detected by comparative analysis of the complex genotypes frequencies which included 8 polymorphic regulatory gene regions of all genes studied. In most genetic complexes associated with the disease development, homozygous TNFα-863СС, homozygous MMP2-1306 ТТ, and MMP9-1562СС genotypes have been detected, together with the combination of homozygous VEGFA+936СС genotype in the same patients. We can assume that harboring allelic variants, which may contribute to angiogenesis prorcesses is typical for the genome of patients with macular degeneration, along with low-level production of pro-inflammatory regulatory factors and enzymes participating in degradation of extracellular matrix. Analysis of complex genetic factors, procing some factors taking part at the pathological process being the regulators of production for each other, is more informative when detecting protective and resistant markers of the disease development rather than single genetic markers, thus being useful for genomic screening.
format article
author A. V. Shevchenko
V. F. Prokofyev
V. I. Konenkov
V. V. Chernykh
A. V. Eremina
L. V. Dudnikova
N. Yu. Kashkina
A. N. Trunov
author_facet A. V. Shevchenko
V. F. Prokofyev
V. I. Konenkov
V. V. Chernykh
A. V. Eremina
L. V. Dudnikova
N. Yu. Kashkina
A. N. Trunov
author_sort A. V. Shevchenko
title NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
title_short NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
title_full NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
title_fullStr NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
title_full_unstemmed NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (ММР2-1306, ММР3-1171, ММР9-1569) GENES IN AGERELATED MACULAR DEGENERATION
title_sort network approach to analysis of quantitative trait loci for tumor necrosis factor (tnfα-863, tnfα-308, tnfα-238), vascular endothelial growth factor (vegf-2578, vegf+936) and matrix metalloproteinase (ммр2-1306, ммр3-1171, ммр9-1569) genes in agerelated macular degeneration
publisher SPb RAACI
publishDate 2017
url https://doaj.org/article/b700cda4be5342e9bbd6ea95a52fead3
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