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Τίτλος – Title
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Συσχέτιση του Πολυμορφισμού – 1639G>A του Γονιδίου VKORC1 (Vitamin K Epoxide Reductase Subunit 1) με την Αρτηριακή Υπέρταση Association Study of Vitamin K Epoxide Reductase Subunit 1 (VKORC1) – 1639G>A Polymorphism with Arterial Hypertension |
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Συγγραφέας – Author
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Απόστολος Σαπουντζής1, Γεωργία Ράγια2, Άννα Ταυρίδου2, Ευάγγελος Γ. Μανωλόπουλος2 1Γαστρεντερολογική Κλινική Πανεπιστημιακού Γενικού Νοσοκομείου Πατρών, Πάτρα, Ρίο, Ελλάς. 2Εργαστήριο Φαρμακολογίας, Ιατρική Σχολή, Δημοκρίτειο Πανεπιστήμιο Θράκης, Αλεξανδρούπολη, Ελλάς Apostolos Sapountzis1, Georgia Ragia2, Anna Tavridou2, Vangelis G. Manolopoulos2 1Gastroenterology Clinic Academic Hospital of Patras, Patra, Hellas; 2Laboratory of Pharmacology Medical School Democritus University of Thrace, Alexandroupolis, Hellas |
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Παραπομπή – Citation
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Σαπουντζής,Α., Ράγια,Γ., Ταυρίδου,Α., Μανωλόπουλος,Ε. : Συσχέτιση του Πολυμορφισμού -1639G>A του Γονιδίου VKORC1 (Vitamin K Epoxide Reductase Subunit 1) με την Αρτηριακή Υπέρταση, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 27: 95-98 (2009)
Sapountzis,A., Ragia,G., Tavridou,A., Manolopoulos,V. : Association Study of Vitamin K Epoxide Reductase Subunit 1 (VKORC1) -1639G>A Polymorphism with Arterial Hypertension, Epitheorese Klin. Farmakol. Farmakokinet. 27: 95-98 (2009)
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Ημερομηνία Δημοσιευσης – Publication Date
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8 Μαρτίου 2009 – 2009-03-08
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Γλώσσα Πλήρους Κειμένου –
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Ελληνικά – Greek |
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Λέξεις κλειδιά – Keywords
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VKORC1, hypertension, gene polymorphism
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Λοιποί Όροι – Other Terms
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Στατιστική Μελέτη Statistical Study |
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Περίληψη – Summary
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– Arterial hypertension is a common multifactorial disease affecting globally more than 30% of population. The genetics of hypertension is a challenging field that remains still unclear. VKORC1 is a major enzyme of vitamin K cycle catalyzing the conversion of vitamin K-epoxide back to vitamin K. Vitamin K dependent proteins are involved in coagulation, calcium metabolism and other physiological mechanisms. Undercar-boxylation of these proteins due to genetic polymorphisms of VKORC1 leads to arterial calcification which is a main cause and a clinical symptom of arterial hypertension. Moreover, VKORC1 is the target of coumarins during anticoagulant therapy and VKORC1 gene polymorphisms are of major importance in anticoagulation pharmacogenetics. The aim of the present study is to explore the association of VKORC1 -1639G>A polymorphism with arterial hypertension. 77 hypertensive and 68 normotensive subjects participated in the study. The participants belonged to the Muslim community of Western Thrace. VKORC1 -1639G>A polymorphism was genotyped with PCR-RFLP method. The frequency of VKORC1 -1639A variant allele was 49.4% in hypertensive subjects compared to 47.8% in normotensive controls and did not differ between two groups (p=0.724). In total of subjects, VKORC1 -1639AA genotype was present at a frequency of 28.3%. In conclusion, we found no association of VKORC1 -1639G>A polymorphism with arterial hypertension. However, a proportion of approximately 30% of the studied population is sensitive to anticoagulant therapy and may need dose adjustment in case of anticoagulant treatment. |
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Αναφορές – References
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1. Ezzati M., et al. Selected major risk factors and global and regional burden of disease. Lancet 360: 1347-60 (2002)
2. Marteau J.B., et al.: Genetic determinants of blood pressure regulation. J. Hypertension 23: 2127-2143 (2005) 3. Garcia A., et al.: VKORC1 and the Vitamin K Cycle. Vitam. Horm. 78: 23-33 (2008) 4. Reider J., et al.: Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. 352: 2285-2293 (2005) 5. Schelleman H., et al.: Ethnic differences in warfarin maintenance dose requirements and its relationship with genetics. Pharmacogenomics 9:1331-1346 (2008) 6. Wang Y., et al.: VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease and aortic dissection). Circulation 113: 1615-1621 (2006) 7. Watzka M., et al.: Functional promoter polymorphism in the VKORC1 gene is no major genetic determinant for coronary heart disease in Northern Germans. Thromb. Haemost. 97: 998-1002 (200) 8. Spronk M.H.: Vitamin K Epoxide reductase complex and vascular calcification. Is this the important link between vitamin K and the arterial vessel wall? Circulation 113: 1550-1552 (2006) 9. 2007 Guidelines for the management of Arterial Hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology. J. Hypert. 25: 1105-1187 (2007) 10. Stergiou G.S., et al.: Validation of the Microlife BPA100 Plus device for self-home blood pressure measurement according to the International Protocol Blood. Blood Press. Monit. 11: 157-160 (2006) 11. Sconce E.A., et al.: The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regiment. Blood 106: 2329-2333 (2005) 12. Oner Ozgon G., et al.: VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients. Eur. J. Clin. Pharmacol. 64: 889-894 (2008) |
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