0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Molecular Variant of the Human Paraoxonase/Arylesterase Gene Is Associated with Central Retinal Vein Occlusion in the Japanese Population

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Central retinal vein occlusion (CRVO) is a complex trait caused by a number of local and systemic factors. Among the latter, atherosclerosis has been attributed a major pathogenic role. Recently, the paraoxonase/arylesterase (PONA) enzyme has been implicated in the pathogenesis of atherosclerosis. There is a 10- to 40-fold variability in the activity of this enzyme among individuals. This variability is due to the presence of an A/G polymorphism in the coding region of the gene. The A and G alleles code for glutamine (A genotype) and arginine (B genotype), respectively. We determined the PONA genotypes and alleles in 42 patients with CRVO and in 45 control subjects of the Japanese population. The distribution of AA, AB and BB genotypes were 9.6, 45.2 and 45.2%, respectively, in the patients and 26.7, 53.3 and 20.0% in the control subjects, respectively (p < 0.05). The A allele frequency was 0.32 in patients and 0.53 in controls (p < 0.01). In conclusion, molecular variants of the PONA gene are involved in the predisposition to CRVO. Further studies are needed to characterize the molecular mechanism by which the PONA enzyme is involved in atherosclerosis.

          Related collections

          Most cited references 2

          • Record: found
          • Abstract: found
          • Article: not found

          Is paraoxonase related to atherosclerosis.

          Human serum paraoxonase is responsible for the hydrolysis of organophosphate anticholinesterases, however, whether the enzyme has a physiological role other than the detoxication of insecticides and nerve gases has remained uncertain. Recently, evidence has begun to accumulate of a relationship between the serum activity of paraoxonase and atherosclerosis. Paraoxonase may a fundamental role in lipoprotein metabolism, preventing oxidative changes to low-density lipoprotein which render the particle atherogenic.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification.

            Human and rabbit paraoxonases/arylesterases were purified to homogeneity by chromatographic and gel electrophoretic/isofocusing procedures coupled with activity stains. N-terminal and peptide sequence analysis suggested retention of the secretion signal sequence and allowed design of oligonucleotide probes. The probes were used to isolate a 1294-bp rabbit paraoxonase cDNA clone, which, in turn, was used to isolate three human cDNA clones. Comparison of rabbit and human protein and cDNA sequences indicated a high degree of sequence conservation (approximately 85% identity) and verified that paraoxonase retains its signal sequence (except for the N-terminal Met). The rabbit cDNA encodes a protein of 359 amino acids and the human a protein of 355 amino acids. In situ hybridization demonstrated, as expected, that the paraoxonase gene maps to the long arm of human chromosome 7. Arginine at position 192 specifies high activity paraoxonase and glutamine low activity human paraoxonase. Variation in protein levels explains the variation of enzyme activity observed within a genetic class. Toxicity studies showed that raising rat plasma paraoxonase levels by i.v. administration of partially purified rabbit paraoxonase protected animals against cholinesterase inhibition by paraoxon and chlorpyrifos oxon. Protection correlated with the relative rates of hydrolysis of these two compounds.
              Bookmark

              Author and article information

              Journal
              OPH
              Ophthalmologica
              10.1159/issn.0030-3755
              Ophthalmologica
              S. Karger AG
              0030-3755
              1423-0267
              1998
              August 1998
              18 June 1998
              : 212
              : 4
              : 257-259
              Affiliations
              Department of Ophthalmology, Yamagata University School of Medicine, Yamagata, Japan
              Article
              27303 Ophthalmologica 1998;212:257–259
              10.1159/000027303
              9672215
              © 1998 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.

              Page count
              Pages: 3
              Categories
              Original Paper · Travail original · Originalarbeit

              Comments

              Comment on this article