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      Renalase Gene Polymorphism in Patients with Hypertension and Concomitant Coronary Heart Disease

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          Abstract

          Background/Aims: This study aimed to investigate renalase gene polymorphism in patients with hypertension and concomitant coronary heart disease (CHD) and to evaluate the risk for CHD in hypertensive patients from the view of genetics. Methods: NCBI and HapMap genome database were employed to screen the Single nucleotide polymorphisms (SNP). These SNPs were detected in hypertensive and CHD patients (n=791), hypertensive patients (n=802) and healthy controls (n=812), and the genotypes were recorded. Haploview 4.2 software was used to determine the genotypes, allele frequency, haplotypes, linkage disequilibrium and Hardy-Weinberg (HWE) equilibrium, and odds ratio (OR) was calculated with non-conditioned logistic regression analysis. Results: The frequency of allele A of rs2576178 in patients with hypertensive and CHD was markedly higher than that in hypertensive patients (p=0.001, OR=1.625,95% CI 1.221-2.160). The frequency of allele C of rs2296545 in hypertensive patients was significantly higher than that in healthy controls (P=0.009, OR=1.436, 95% CI 1.095-1.883). Conclusion: The allele A of rs2576178 may be a predisposing factor of CHD in hypertensive patients, and hypertensive patients with AA genotype are susceptible to develop CHD. The allele C of rs2296545 may be a predisposing factor of hypertension and patients with CC genotype are susceptible to develop hypertension.

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          Most cited references23

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          Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure.

          The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.
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            Estimation and Tests of Haplotype-Environment Interaction when Linkage Phase Is Ambiguous

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              Renalase deficiency aggravates ischemic myocardial damage.

              Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD. © 2011 International Society of Nephrology
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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
                2014
                July 2014
                30 April 2014
                : 39
                : 1
                : 9-16
                Affiliations
                Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
                Author notes
                *Weihong Jiang, Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South, University, Changsha, Hunan 410013 (China), E-Mail jiangweihongdoc@163.com
                Article
                355771 Kidney Blood Press Res 2014;39:9-16
                10.1159/000355771
                24821235
                6c8d2336-0a12-4a58-8b08-2e827d6d73d4
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. 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
                : 28 March 2014
                Page count
                Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Hypertension,Coronary heart disease,Renalase,Genotype
                Cardiovascular Medicine, Nephrology
                Hypertension, Coronary heart disease, Renalase, Genotype

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