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      An Erythropoietin Gene Polymorphism in the Hypoxia-Responsive Element at Position 3434 Is Possibly Associated with Hypertension

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          Abstract

          Background/Aims: Several polymorphisms of vasoactive hormones have been implicated in hypertension. Erythropoietin (EPO) interacts with vasoactive substances, such as angiotensin II. Previously detected single nucleotide polymorphisms in the hypoxia-responsive element of EPO might be associated with hypertension and hypertensive end organ damages. Methods: 400 hypertensive patients and 200 age- and gender-matched normotensive controls were genotyped for an EPO polymorphism [cytosine (C)/thymine (T) single nucleotide polymorphism] at position 3434. Patients were grouped according to their genotype into the CC group (CC genotype) and the CT/TT group (CT and TT genotype). BP was measured by ambulatory BP monitoring. Results: The CC genotype was present in 87% of hypertensive patients and in 78.5% of controls (p = 0.007). In addition, patients with the CC genotype had higher BP levels compared with CT/TT genotypes (BPsys 143.7 ± 20.4 vs. 136.1 ± 13.5 mm Hg, p = 0.01, and BPdias 85.8 ± 11.6 vs. 82.4 ± 8.9, p = 0.043) despite a nearly identical number of antihypertensive drugs (2.3 ± 1.5 vs. 2.3 ± 1.6; p = 0.257). 100% of the small number of patients with end-stage renal disease (n = 15) had the CC genotype. Conclusion: The CC genotype of the EPO gene at position 3434 is more frequently found in patients with hypertension and is associated with higher BP levels.

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          Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression.

          Although it was known for a long time that oxygen deprivation leads to the transcriptional induction of the gene encoding erythropoietin, the molecular mechanisms behind this process remained enigmatic. The cloning of the hypoxia-inducible factors (HIFs), the finding that HIF-1 regulates the expression of many more genes apart from erythropoietin, and the elucidation of the oxygen-dependent mechanisms degrading the HIF alpha subunits recently led to the spectacular discovery of the molecular principles of oxygen sensing. This review aims to summarize our current knowledge of oxygen-regulated gene expression..
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            Fluorescence detection in automated DNA sequence analysis.

            We have developed a method for the partial automation of DNA sequence analysis. Fluorescence detection of the DNA fragments is accomplished by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymatic DNA sequence analysis. A different coloured fluorophore is used for each of the reactions specific for the bases A, C, G and T. The reaction mixtures are combined and co-electrophoresed down a single polyacrylamide gel tube, the separated fluorescent bands of DNA are detected near the bottom of the tube, and the sequence information is acquired directly by computer.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2012
                March 2012
                07 September 2011
                : 35
                : 2
                : 71-76
                Affiliations
                aCenter of Nephrology Göttingen, Hypertension Care and Research Unit, and bDepartment of Anaesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, and cClinic for Nephrology, Hannover Medical School, Hannover, Germany; dDepartment of Cardiology, University Hospital Zurich, and eDepartment of Biostatistics, University of Zurich, Zurich, Switzerland; fDepartment of Cardiothoracic Transplantation and Mechanical Support, Royal Brompton and Harefield Hospitals, London, UK
                Author notes
                *Egbert Godehard Schulz, MD, Center of Nephrology Göttingen, An der Lutter 24, DE–37075 Göttingen (Germany), Tel. +49 551 508 760, E-Mail eg.schulz@goedia.de
                Article
                330245 Kidney Blood Press Res 2012;35:71–76
                10.1159/000330245
                21912181
                4613e36f-4e06-4999-836a-867040e12012
                © 2011 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 18 March 2011
                : 10 June 2011
                Page count
                Tables: 3, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Hypertension,Erythropoietin polymorphism,Genetics,End organ damage,Hypoxia-responsive element,Ambulatory blood pressure monitoring

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