medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2016-1-12-21medsovet-3Research ArticleЗДОРОВЫЙ РЕБЕНОКHEALTHY CHILDПолногеномный анализ сайтов связывания рецептора витамина D указывает на широкий спектр потенциальных применений витамина D в терапииThe genome-wide analysis of the vitamin D receptor binding sites evidences a wide range of potential therapeutic applications of vitamin DГромоваО. А.GromovaO. A.noemail@neicon.ruТоршинИ. Ю.TorshinI. Y.noemail@neicon.ruСпиричевВ. Б.SpirichevV. B.noemail@neicon.ruИвановская государственная медицинская академияРоссияIvanovo State Medical AcademyRussian FederationМосковский физико-технический институт (государственный университет)РоссияMoscow Institute of Physics and TechnologyRussian FederationНаучно-исследовательский институт питанияРоссияScientific Research Institute of NutritionRussian Federation201630122016111221Copyright © Громова О.А., Торшин И.Ю., Спиричев В.Б., 20162016Громова О.А., Торшин И.Ю., Спиричев В.Б.Gromova O.A., Torshin I.Y., Spirichev V.B.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/3

В настоящей работе представлены результаты полногеномного биоинформационного анализа взаимодействий рецептора витамина D с ДНК генома человека. Методами системно-биологического анализа проведен анализ биологических ролей белков, которые специфически ассоциированы с воздействием рецептора VDR. Систематизация биологических ролей витамина D указывает на широкие и ранее не изученные перспективы педиатрических применений препаратов витамина D для профилактики и терапии широкого круга заболеваний с периода внутриутробного развития и раннего детства.

The article presents the results of the genome-wide bioinformatic analysis of the vitamin D receptor interactions with the human genome DNA. Using a biological system assay, biological roles of proteins were analyzed that are specifically associated with the impact of VDR receptor. Systematization of the biological roles of vitamin D opens broad and previously unexplored perspectives for pediatric applications of vitamin D preparations for the prevention and treatment of a wide range of diseases starting from the fetal stage and early childhood.

геномные эффекты витамина Dэпигенетикадетипрофилактика дефицита витамина Dgenomic effects of vitamin Depigeneticschildrenprevention of vitamin D deficiencyReferencesJohnson DS, Mortazavi A. Genome-wide mapping of in vivo protein-DNA interactions. Science 2007. 316: 1497-1502.Johnson DS, Mortazavi A. Genome-wide mapping of in vivo protein-DNA interactions. Science 2007. 316: 1497-1502.Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE. A ChlP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010, 20(10): 1352-60.Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE. A ChlP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010, 20(10): 1352-60.Heikkinen S, Vaisanen S, Pehkonen P, Seuter S, Benes V, Carlberg C. Nuclear hormone 1alpha,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy. Nucleic Acids Res. 2011, 39(21): 9181-93.Heikkinen S, Vaisanen S, Pehkonen P, Seuter S, Benes V, Carlberg C. Nuclear hormone 1alpha,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy. Nucleic Acids Res. 2011, 39(21): 9181-93.Ding N, Yu RT, Subramaniam N, Sherman MH, Wilson C, Rao R, Leblanc M. A vitamin D recep-tor/SMAD genomic circuit gates hepatic fibrotic response. Cell. 2013, 153(3): 601-13.Ding N, Yu RT, Subramaniam N, Sherman MH, Wilson C, Rao R, Leblanc M. A vitamin D recep-tor/SMAD genomic circuit gates hepatic fibrotic response. Cell. 2013, 153(3): 601-13.Torshin lYu. Sensing the change from molecular genetics to personalized medicine. Nova Biomedical Books, NY, USA, 2009, In Bioinformatics in the Post-Genomic Era series, lSBN 1-60692-217-0.Torshin lYu. Sensing the change from molecular genetics to personalized medicine. Nova Biomedical Books, NY, USA, 2009, In Bioinformatics in the Post-Genomic Era series, lSBN 1-60692-217-0.Громова ОА., Торшин И.Ю., Лиманова О.А., Гришина Т.Р., Громов А.Н. Обеспеченность витамином D и метаболические нарушения: систематический анализ фундаментальных и доказательных исследований по проблемам избыточной массы тела и сахарного диабета. Фарматека, 2014 (20): 27-38.Громова ОА., Торшин И.Ю., Лиманова О.А., Гришина Т.Р., Громов А.Н. Обеспеченность витамином D и метаболические нарушения: систематический анализ фундаментальных и доказательных исследований по проблемам избыточной массы тела и сахарного диабета. Фарматека, 2014 (20): 27-38.Garten A, Schuster S, Kiess W. The insulin-like growth factors in adipogenesis and obesity. Endocrinol Metab Clin North Am. 2012, 41(2): 283-95.Garten A, Schuster S, Kiess W. The insulin-like growth factors in adipogenesis and obesity. Endocrinol Metab Clin North Am. 2012, 41(2): 283-95.Conover CA, Mason MA, Bale LK, Harrington SC, Nyegaard M, Oxvig C, Overgaard MT. Transgenic overexpression of pregnancy-associated plasma protein-A in murine arterial smooth muscle accelerates atherosclerotic lesion development. Am J Physiol Heart Circ Physiol. 2010, 299(2): H284-91.Conover CA, Mason MA, Bale LK, Harrington SC, Nyegaard M, Oxvig C, Overgaard MT. Transgenic overexpression of pregnancy-associated plasma protein-A in murine arterial smooth muscle accelerates atherosclerotic lesion development. Am J Physiol Heart Circ Physiol. 2010, 299(2): H284-91.Boldt HB, Bale LK, Resch ZT, Oxvig C, Overgaard MT, Conover CA. Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic lesion development in mice. Endocrinology. 2013, 154(1): 246-52.Boldt HB, Bale LK, Resch ZT, Oxvig C, Overgaard MT, Conover CA. Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic lesion development in mice. Endocrinology. 2013, 154(1): 246-52.Moursi AM, Winnard PL, Winnard AV, Rubenstrunk JM, Mooney MP. Fibroblast growth factor 2 induces increased calvarial osteoblast proliferation and cranial suture fusion. Cleft Palate CraniofacJ. 2002, 39(5): 487-496.Moursi AM, Winnard PL, Winnard AV, Rubenstrunk JM, Mooney MP. Fibroblast growth factor 2 induces increased calvarial osteoblast proliferation and cranial suture fusion. Cleft Palate CraniofacJ. 2002, 39(5): 487-496.Zhang X, Ibrahimi OA, Olsen SK. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006, 281(23): 15694-700.Zhang X, Ibrahimi OA, Olsen SK. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006, 281(23): 15694-700.Lee JG, Kay EP. FGF-2-induced wound healing in corneal endothelial cells requires Cdc42 activation and Rho inactivation through the phosphatidylinositol 3-kinase pathway. Invest Ophthalmol Vis Sci. 2006, 47(4): 1376-1386.Lee JG, Kay EP. FGF-2-induced wound healing in corneal endothelial cells requires Cdc42 activation and Rho inactivation through the phosphatidylinositol 3-kinase pathway. Invest Ophthalmol Vis Sci. 2006, 47(4): 1376-1386.Lin A, Hokugo A, Choi J, Nishimura I. Small cytoskeleton-associated molecule, fibroblast growth factor receptor 1 oncogene partner 2/ wound inducible transcript-3.0 (FGFR1OP2/ wit3.0), facilitates fibroblast-driven wound closure. Am J Pathol. 2010, 176(1): 108-21.Lin A, Hokugo A, Choi J, Nishimura I. Small cytoskeleton-associated molecule, fibroblast growth factor receptor 1 oncogene partner 2/ wound inducible transcript-3.0 (FGFR1OP2/ wit3.0), facilitates fibroblast-driven wound closure. Am J Pathol. 2010, 176(1): 108-21.Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011, 96(7): 1911-30.Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011, 96(7): 1911-30.Oyama N, Iwatsuki K, Satoh M, Akiba H, Kaneko F. Dermal fibroblasts are one of the therapeutic targets for topical application of 1alpha,25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-beta induction. Br J Dermatol. 2000, 143(6): 1140-1148.Oyama N, Iwatsuki K, Satoh M, Akiba H, Kaneko F. Dermal fibroblasts are one of the therapeutic targets for topical application of 1alpha,25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-beta induction. Br J Dermatol. 2000, 143(6): 1140-1148.Inoue K, Aoi N, Yamauchi Y, Sato T, Suga H, Eto H, Kato H, Tabata Y, Yoshimura K. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis. J Cell Mol Med. 2009, 13(11-12): 4643-56.Inoue K, Aoi N, Yamauchi Y, Sato T, Suga H, Eto H, Kato H, Tabata Y, Yoshimura K. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis. J Cell Mol Med. 2009, 13(11-12): 4643-56.Kinoshita A, Fukumaki Y, Shirahama S, Miyahara A, Nishimura G. TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations. Am J Med Genet A. 2004, 127A(1): 104-107.Kinoshita A, Fukumaki Y, Shirahama S, Miyahara A, Nishimura G. TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations. Am J Med Genet A. 2004, 127A(1): 104-107.Loeys BL. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005, 37(3): 275-81.Loeys BL. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005, 37(3): 275-81.Luderer HF, Nazarian RM, Zhu ED, Demay MB. Ligand-dependent actions of the vitamin D receptor are required for activation of TGF-beta signaling during the inflammatory response to cutaneous injury. Endocrinology. 2013, 154(1): 16-24.Luderer HF, Nazarian RM, Zhu ED, Demay MB. Ligand-dependent actions of the vitamin D receptor are required for activation of TGF-beta signaling during the inflammatory response to cutaneous injury. Endocrinology. 2013, 154(1): 16-24.Szeto FL, Sun J, Kong J, Duan Y. Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol. 2007, 103(3-5): 563-6.Szeto FL, Sun J, Kong J, Duan Y. Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol. 2007, 103(3-5): 563-6.Reinholz M, Schauber J. [Vitamin D and innate immunity of the skin]. Dtsch Med Wochenschr. 2012, 137(46): 2385-9.Reinholz M, Schauber J. [Vitamin D and innate immunity of the skin]. Dtsch Med Wochenschr. 2012, 137(46): 2385-9.Segaert S. Vitamin D regulation of cathelicidin in the skin: toward a renaissance of vitamin D in dermatology? J Invest Dermatol. 2008, 128(4): 773-5.Segaert S. Vitamin D regulation of cathelicidin in the skin: toward a renaissance of vitamin D in dermatology? J Invest Dermatol. 2008, 128(4): 773-5.Muehleisen B, Bikle DD, Aguilera C, Burton DW, Sen GL, Deftos LI, Gallo RL. PTH/PTHrP and vitamin D control antimicrobial peptide expression and susceptibility to bacterial skin infection. Sci Transl Med. 2012, 4(135): 135ra66.Muehleisen B, Bikle DD, Aguilera C, Burton DW, Sen GL, Deftos LI, Gallo RL. PTH/PTHrP and vitamin D control antimicrobial peptide expression and susceptibility to bacterial skin infection. Sci Transl Med. 2012, 4(135): 135ra66.Burkiewicz CJ, Guadagnin FA, Skare TL, do Nascimento MM, Servin SC, de Souza GD. Vitamin D and skin repair: a prospective, double-blind and placebo controlled study in the healing of leg ulcers. Rev Col Bras Cir. 2012, 39(5): 401-407.Burkiewicz CJ, Guadagnin FA, Skare TL, do Nascimento MM, Servin SC, de Souza GD. Vitamin D and skin repair: a prospective, double-blind and placebo controlled study in the healing of leg ulcers. Rev Col Bras Cir. 2012, 39(5): 401-407.Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, Giannobile WV, McCauley LK. The impact of vitamin D status on perio-dontal surgery outcomes. J Dent Res. 2011, 90(8): 1007-12.Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, Giannobile WV, McCauley LK. The impact of vitamin D status on perio-dontal surgery outcomes. J Dent Res. 2011, 90(8): 1007-12.Захарова И.Н., Мальцев С.В., Боровик Т.Э. с соавт. Недостаточность витамина D у детей раннего возраста в России (результаты многоцентрового исследования - зима 20132014 гг.). Педиатрия им. ГН. Сперанского. 2014, 93 (2): 75-80.Захарова И.Н., Мальцев С.В., Боровик Т.Э. с соавт. Недостаточность витамина D у детей раннего возраста в России (результаты многоцентрового исследования - зима 20132014 гг.). Педиатрия им. ГН. Сперанского. 2014, 93 (2): 75-80.Торшин И.Ю., Громова О.А., Лиманова О.А. и др. Обеспеченность витамином D детей и подростков 7-14 лет и взаимосвязь дефицита витамина D с нарушениями здоровья детей. Анализ крупномасштабной выборки пациентов посредством интеллектуального анализа данных. Педиатрия им. ГН. Сперанского, 2015, 94 (2): 175-184.Торшин И.Ю., Громова О.А., Лиманова О.А. и др. Обеспеченность витамином D детей и подростков 7-14 лет и взаимосвязь дефицита витамина D с нарушениями здоровья детей. Анализ крупномасштабной выборки пациентов посредством интеллектуального анализа данных. Педиатрия им. ГН. Сперанского, 2015, 94 (2): 175-184.Описание Аквадетрим. Энциклопедия РЛС http: //www.rlsnet.ru/tn_index_id_24362.htm.Описание Аквадетрим. Энциклопедия РЛС http: //www.rlsnet.ru/tn_index_id_24362.htm.Громова О.А., Торшин И.Ю., Захарова И.Н. и др. О дозировании витамина D у детей и подростков. Вопросы современной педиатрии, 2015, 14(1): 38-47.Громова О.А., Торшин И.Ю., Захарова И.Н. и др. О дозировании витамина D у детей и подростков. Вопросы современной педиатрии, 2015, 14(1): 38-47.

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