Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors

Victor R GordeukLydia A Polyakova


Adaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C>T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C>T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C>T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P <.0005), as well as premature mortality related to cerebral vascular events and peripheral thrombosis. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL syndrome were not found, suggesting that overexpression of HIF-1alpha and VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted ser...Continue Reading


May 1, 1982·The American Journal of Clinical Nutrition·J D Cook, B S Skikne
Jun 30, 1995·Science·Jaroslav F PrchalL Sokol
Dec 24, 1997·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M LosEmile E Voest
Dec 31, 1997·The Journal of Clinical Investigation·T Michel, O Feron
Mar 5, 1998·The American Journal of Physiology·L A PalmerR A Johns
Sep 16, 1998·Journal of Vascular Surgery·S S ShoabP D Coleridge-Smith
Jan 23, 1999·Plastic and Reconstructive Surgery·J ChangA E Turk
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·Volker H HaaseR Jaenisch
Aug 23, 2001·Trends in Molecular Medicine·Gregg L Semenza
Jan 25, 2002·Genes, Chromosomes & Cancer·Jeffrey W WalterDouglas A Marchuk
May 4, 2002·Blood Cells, Molecules & Diseases·Sonny O AngJosef T Prchal
Oct 24, 2002·Blood·Jerry L Spivak
Nov 5, 2002·Nature Genetics·Sonny O AngJosef T Prchal
Jan 14, 2003·Experimental Biology and Medicine·James W Fisher
Mar 6, 2003·The Journal of Clinical Investigation·Aernout Luttun, Peter Carmeliet
Jun 20, 2003·Lancet·Russell R LonserEdward H Oldfield
Jul 5, 2003·American Journal of Human Genetics·Yves PastoreJosef T Prchal
Feb 28, 2004·Expert Reviews in Molecular Medicine·F M Richards


Feb 9, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Donghoon YoonVictor R Gordeuk
Sep 28, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Donald A McClainVictor R Gordeuk
Jun 26, 2008·Annals of Hematology·Jecko Thachil
Mar 10, 2011·European Journal of Human Genetics : EJHG·Eamonn R MaherStéphane Richard
Jun 21, 2005·Nature Reviews. Cancer·Jerry L Spivak
Jan 24, 2009·Nature Reviews. Drug Discovery·Peter FraislPeter Carmeliet
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cynthia M BeallYong Tang Zheng
Sep 17, 2009·Antioxidants & Redox Signaling·Simon NagelChristopher J Schofield
Jun 16, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samuel M CohenJon C Cook
Apr 28, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kay A CriswellTimothy Anderson
Mar 11, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Federico FormentiPeter A Robbins
Jun 26, 2004·Journal of Pediatric Hematology/oncology·Tom Van MaerkenJoris Verlooy
Feb 24, 2005·Current Opinion in Hematology·Josef T Prchal
Jul 27, 2004·Current Opinion in Pediatrics·Yong-hui Jiang, Arthur L Beaudet
Feb 9, 2013·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Maurizio ZangariJosef T Prchal
Sep 28, 2006·Clinical and Experimental Pharmacology & Physiology·Christian Stockmann, Joachim Fandrey
Mar 9, 2007·Postgraduate Medical Journal·Jeremy S Windsor, George W Rodway
Nov 28, 2007·Annual Review of Pathology·Tony E Walshe, Patricia A D'Amore
Nov 28, 2007·Annual Review of Pathology·William Kaelin
May 7, 2010·American Journal of Physiology. Renal Physiology·Volker H Haase
Jun 9, 2007·The Journal of Clinical Investigation·Carole PeyssonnauxRandall S Johnson
Mar 4, 2010·The Journal of Clinical Investigation·Michele M HickeyM C Simon
Dec 17, 2009·Hematology·Mary Frances McMullin
Aug 1, 2012·Biologics : Targets & Therapy·Steve Elliott, Angus M Sinclair
Dec 18, 2013·Annals of Hematology·Steve ElliottWolfgang Jelkmann
Jun 14, 2006·PLoS Medicine·Thomas G SmithPeter A Robbins
Sep 3, 2013·Blood Cells, Molecules & Diseases·Xu ZhangVictor R Gordeuk
Jan 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Melanie J PercyFrank S Lee
Oct 26, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Eric BachmanShalender Bhasin
Oct 14, 2010·Annual Review of Pathology·Frank S Lee, Melanie J Percy
Sep 6, 2014·Best Practice & Research. Clinical Haematology·Wan-Jen Hong, Jason Gotlib
Mar 20, 2009·Leukemia·M M Patnaik, Ayalew Tefferi
Jun 8, 2012·FEBS Letters·Hannah L Bader, Tien Hsu
Nov 19, 2010·Expert Review of Hematology·Mary Frances McMullin
Dec 22, 2007·Expert Review of Anticancer Therapy·W K Rathmell, Shufen Chen
Dec 15, 2015·Nature Reviews. Nephrology·Patrick H Maxwell, Kai-Uwe Eckardt
Feb 2, 2016·La Revue de médecine interne·T BarbaM Pavic
Dec 4, 2012·Best Practice & Research. Clinical Haematology·Josef T Prchal
Nov 9, 2015·Annals of Hematology·Maria Luigia RandiFabrizio Fabris
Apr 3, 2012·Hematology/oncology Clinics of North America·Marina KremyanskayaRonald Hoffman
Sep 24, 2008·Seminars in Hematology·Neeraj Agarwal, Josef T Prchal
Mar 18, 2008·Biochimica Et Biophysica Acta·Dorus A MansRachel H Giles
Jul 28, 2007·Critical Reviews in Oncology/hematology·Vivien M HodgesA Peter Maxwell
Feb 6, 2007·Seminars in Nephrology·Henry N Hulter, Reto Krapf
Mar 6, 2007·Advances in Enzyme Regulation·Serafim KiriakidisPatrick H Maxwell
Oct 23, 2009·The British Journal of Surgery·C S Lim, A H Davies
Oct 25, 2006·Journal of Thrombosis and Haemostasis : JTH·D ColaizzoM Margaglione
Jun 25, 2005·Journal of Thrombosis and Haemostasis : JTH·W K Rathmell, M C Simon
Nov 14, 2008·American Journal of Hematology·Melanie J Percy, Elisa Rumi
Oct 7, 2006·Human Mutation·Kai Ren OngEamonn R Maher
May 20, 2008·Hematological Oncology·Elisa Rumi
Dec 13, 2006·British Journal of Haematology·Marcello Di NisioEuropean Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Investigators
Apr 16, 2008·British Journal of Haematology·Thomas G SmithPeter Ratcliffe
Dec 9, 2008·American Journal of Hematology·Xiaomei NiuVictor R Gordeuk
Oct 4, 2007·Experimental Physiology·Chun LiuPeter A Robbins
Feb 14, 2009·American Journal of Medical Genetics. Part a·James C BartonCatherine A Stolle
Oct 12, 2013·Human Mutation·Celeste BentoECE-Consortium
Feb 3, 2005·International Immunopharmacology·John J Haddad, Hisham L Harb
Jun 20, 2006·Best Practice & Research. Clinical Haematology·Guido FinazziJosef T Prchal
Apr 11, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Ishmael KasvosveVictor R Gordeuk
Jun 9, 2015·Experimental Physiology·Ri-Li GeDonald A McClain
Sep 13, 2005·Biochemical and Biophysical Research Communications·William Kaelin
Mar 4, 2015·British Journal of Haematology·Mary Frances McMullinHolger Cario
Jan 15, 2015·Pediatric Blood & Cancer·Alpa SidhuMichael U Callaghan
Dec 24, 2013·Genetics Research International·Carla Luana DinardoAlexandre Costa Pereira
Jan 8, 2013·Blood Reviews·Volker H Haase
Apr 4, 2015·European Journal of Internal Medicine·Grace Lee, Murat O Arcasoy
Jan 27, 2012·Journal of Vascular Surgery·Chung S LimAlun H Davies
May 24, 2008·Molecular Cell·William Kaelin, Peter Ratcliffe
Jun 5, 2013·Blood·Kristin FrankeBen Wielockx
Dec 3, 2014·Annals of Vascular Surgery·Oliwia Anna SegietRomuald Wojnicz
Jan 13, 2015·Blood·Adelina I SergueevaVictor R Gordeuk
May 11, 2016·International Journal of Laboratory Hematology·Mary Frances McMullin
Jan 31, 2016·Spine·Viviane SlonIsrael Hershkovitz
Jul 18, 2016·Current Hematologic Malignancy Reports·Mary Frances McMullin
Sep 18, 2016·La Revue de médecine interne·O Mangin
May 2, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neeraj AgarwalJosef T Prchal
Mar 7, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sara CapodimontiLuigi M Larocca
Apr 27, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sarah M NielsenRachel H Giles
Apr 28, 2017·Hemodialysis International·Volker H Haase
Apr 23, 2013·Therapeutic Advances in Hematology·Mary Frances McMullin
Mar 10, 2018·Chemical Communications : Chem Comm·Martine I AbboudChristopher J Schofield
Feb 1, 2018·International Journal of Molecular Sciences·Joshua M KaplanSean Dikdan
Feb 27, 2018·The Journal of Clinical Investigation·Manik C GhoshTracey A Rouault
Dec 30, 2017·Journal of Paediatrics and Child Health·Joyce Ching Mei LamChris Barnes
May 10, 2018·International Journal of Laboratory Hematology·Celeste Bento
Jul 17, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Mary SlingoPeter A Robbins
May 10, 2017·Thorax·Liza BotrosAnton Vonk Noordegraaf
Mar 16, 2016·Molecular and Cellular Biology·Pinelopi P KapitsinouVolker H Haase
Aug 17, 2012·Circulation. Cardiovascular Genetics·Muzaffar A AnwarAlun H Davies
Mar 24, 2006·American Journal of Physiology. Renal Physiology·Volker H Haase
May 4, 2013·The Journal of Biological Chemistry·Qiulin TanFrank S Lee
Mar 4, 2011·American Journal of Physiology. Cell Physiology·Donghoon YoonJosef T Prchal
Feb 27, 2020·The New England Journal of Medicine·Silverio PerrottaFulvio Della Ragione
Oct 1, 2019·Current Opinion in Nephrology and Hypertension·Gearoid M McMahon, Ajay K Singh
Jul 1, 2020·American Journal of Hematology·Naseema GangatAyalew Tefferi
Mar 23, 2018·Biomedicines·Jing Zhang, Qing Zhang
Mar 24, 2017·Yonsei Medical Journal·Sang Yong ShinHoon Gu Kim
Dec 3, 2005·Cancer Research·Sven GläskerAlexander O Vortmeyer
Jan 16, 2021·Free Radical Biology & Medicine·Danchen WuStephen L Archer

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