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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| Format: | Article |
| Language: | Russian |
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2017-10-01
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| Series: | Медицинская иммунология |
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| Online Access: | https://www.mimmun.ru/mimmun/article/view/1353 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-b700cda4be5342e9bbd6ea95a52fead3 |
| institution | Matheson Library |
| issn | 1563-0625 2313-741X |
| language | Russian |
| publishDate | 2017-10-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj-art-b700cda4be5342e9bbd6ea95a52fead32025-08-04T14:30:35ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2017-10-0119553754610.15789/1563-0625-2017-5-537-546949NETWORK 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 DEGENERATIONA. V. Shevchenko0V. F. Prokofyev1V. I. Konenkov2V. V. Chernykh3A. V. Eremina4L. V. Dudnikova5N. Yu. Kashkina6A. N. Trunov7Research Institute of Clinical and Experimental Lymрhology.Research Institute of Clinical and Experimental Lymрhology.Research Institute of Clinical and Experimental Lymрhology.S. Fyodorov Intersectoral Research and Technology Eye Microsurgery Complex, Novosibirsk Branch.S. Fyodorov Intersectoral Research and Technology Eye Microsurgery Complex, Novosibirsk Branch.S. Fyodorov Intersectoral Research and Technology Eye Microsurgery Complex, Novosibirsk Branch.S. Fyodorov Intersectoral Research and Technology Eye Microsurgery Complex, Novosibirsk Branch.S. Fyodorov Intersectoral Research and Technology Eye Microsurgery Complex, Novosibirsk Branch.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.https://www.mimmun.ru/mimmun/article/view/1353age-related macular degenerationpolymorphism tnfvegf polymorphismммр polymorphismnetwork analysis |
| spellingShingle | 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 Медицинская иммунология age-related macular degeneration polymorphism tnf vegf polymorphism ммр polymorphism network analysis |
| 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_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_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_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 |
| topic | age-related macular degeneration polymorphism tnf vegf polymorphism ммр polymorphism network analysis |
| url | https://www.mimmun.ru/mimmun/article/view/1353 |
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