Blog
About

5
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Norepinephrine Transporter Gene (NET) Polymorphism in Patients with Type 2 Diabetes

      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

          Background: Norepinephrine transporter (NET) is involved in the regulation of norepinephrine (NE) turnover and metabolism. Neuronal NE reuptake may be impaired in individuals with renal disease and/or hypertension due to dysfunction of the NE transporter. A silent G1287A nucleotide substitution in exon 9 of the NET gene was studied in human conditions involving hypertension. We investigated its effect in patients with type 2 diabetes. Methods: The study involved 215 type 2 diabetes patients with nephropathy, 95 patients with diabetes duration ≧10 years, free of nephropathy, and 360 healthy subjects. All individuals were genotyped for the NET-8 gene polymorphism with the PCR-RFLP method. Genotype and allele frequencies were compared between the groups. NE was measured by high-performance liquid chromatography and electrochemical detection. Results: We genotyped 310 patients and 360 controls for the NET gene polymorphism. Genotype distribution in both groups was in accordance with the Hardy-Weinberg equilibrium. There were no significant differences in the frequency of genotypes and alleles between patients and controls (p = 0.43). The frequencies were also similar for patients with nephropathy and those without. After dividing the patient group into hypertensive (n = 208) and normotensive (n = 102) subjects, there was a significant increase in the frequency of the AA genotype in patients with hypertension compared to normotensives (19 vs. 10%, p < 0.05). Conclusion: No association was found between G1287A polymorphism in the NET gene and diabetes. Our results suggest that this polymorphism has a possible role in increased susceptibility to hypertension in patients with type 2 diabetes.

          Related collections

          Most cited references 21

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

          Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6.

          The SLC6 family is a diverse set of transporters that mediate solute translocation across cell plasma membranes by coupling solute transport to the cotransport of sodium and chloride down their electrochemical gradients. These transporters probably have 12 transmembrane domains, with cytoplasmic N- and C-terminal tails, and at least some may function as homo-oligomers. Family members include the transporters for the inhibitory neurotransmitters GABA and glycine, the aminergic transmitters norepinephrine, serotonin, and dopamine, the osmolytes betaine and taurine, the amino acid proline, and the metabolic compound creatine. In addition, this family includes a system B(0+) cationic and neutral amino acid transporter, and two transporters for which the solutes are unknown. In general, SLC6 transporters act to regulate the level of extracellular solute concentrations. In the central and the peripheral nervous system, these transporters can regulate signaling among neurons, are the sites of action of various drugs of abuse, and naturally occurring mutations in several of these proteins are associated with a variety of neurological disorders. For example, transgenic animals lacking specific aminergic transporters show profoundly disturbed behavioral phenotypes and probably represent excellent systems for investigating psychiatric disease. SLC6 transporters are also found in many non-neural tissues, including kidney, intestine, and testis, consistent with their diverse physiological roles. Transporters in this family represent attractive therapeutic targets because they are subject to multiple forms of regulation by many different signaling cascades, and because a number of pharmacological agents have been identified that act specifically on these proteins.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.

            At most synapses, chemical signalling is terminated by a rapid reaccumulation of neurotransmitter into presynaptic terminals. Uptake systems for the biogenic amines are the initial site of action for therapeutic antidepressants and drugs such as cocaine and the amphetamines. We have isolated a complementary DNA clone encoding a human noradrenaline transporter. The cDNA sequence predicts a protein of 617 amino acids, with 12-13 highly hydrophobic regions compatible with membrane-spanning domains. Expression of the cDNA clone in transfected HeLa cells indicates that noradrenaline transport activity is sodium-dependent and sensitive to selective noradrenaline transport inhibitors. Transporter RNA is localized to the brainstem and the adrenal gland. The predicted protein sequence demonstrates significant amino-acid identity with the Na+/gamma-aminobutyric acid transporter, thus identifying a new gene family for neurotransmitter transporter proteins. Analysis of its structure and function may lead to structure-based drug design for the treatment of human depression and could help determine whether transporter abnormalities underlie affective disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Monoamine transporters: from genes to behavior.

              Modulation of fast neurotransmission by monoamines is critically involved in numerous physiological functions and pathological conditions. Plasma membrane monoamine transporters provide one of the most efficient mechanisms controlling functional extracellular monoamine concentrations. These transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET), which are expressed selectively on the corresponding neurons, are established targets of many psychostimulants, antidepressants, and neurotoxins. Recently, genetic animal models with targeted disruption of these transporters have become available. These mice have provided opportunities to investigate the functional importance of transporters in homeostatic control of monoaminergic transmission and to evaluate, in an in vivo model system, their roles in physiology and pathology. The use of these mice as test subjects has been helpful in resolving several important issues on specificity and mechanisms of action of certain pharmacological agents. In the present review, we summarize recent advances in understanding the physiology and pharmacology of monoamine transporters gained in mice with targeted genetic deletion of DAT, SERT, and NET.
                Bookmark

                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
                2006
                January 2007
                16 January 2007
                : 29
                : 6
                : 338-343
                Affiliations
                Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, Skubiszewski Medical University, Lublin, Poland
                Article
                97356 Kidney Blood Press Res 2006;29:338–343
                10.1159/000097356
                17124432
                © 2006 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
                Figures: 1, Tables: 3, References: 31, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/97356
                Categories
                Original Paper

                Comments

                Comment on this article