Multilocus Analysis of Hypertension: A Hierarchical Approach (original) (raw)
Article navigation
Review Articles| May 07 2004
aDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tenn.,
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
cDepartment of Microbiology, Meharry Medical College, Nashville, Tenn.,
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
aDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
cDepartment of Microbiology, Meharry Medical College, Nashville, Tenn.,
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
eBioventures, Murfreesboro, Tenn.,
Search for other works by this author on:
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
cDepartment of Microbiology, Meharry Medical College, Nashville, Tenn.,
Search for other works by this author on:
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
dDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
iDepartment of Medicine and Therapeutics, University of Ghana, Accra, Ghana
Search for other works by this author on:
iDepartment of Medicine and Therapeutics, University of Ghana, Accra, Ghana
Search for other works by this author on:
fInstitute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, D.C.,
Search for other works by this author on:
gDepartment of Pathology, Medical Automation Research Center, University of Virginia, Charlottesville, Va., and
Search for other works by this author on:
hDepartments of Pediatrics and Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C., USA;
Search for other works by this author on:
bProgram in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn.,
Search for other works by this author on:
Hum Hered (2004) 57 (1): 28–38.
Citation
Scott M. Williams, Marylyn D. Ritchie, John A. Phillips III, Elliot Dawson, Melissa Prince, Elvira Dzhura, Alecia Willis, Amma Semenya, Marshall Summar, Bill C. White, Jonathan H. Addy, John Kpodonu, Lee-Jun Wong, Robin A. Felder, Pedro A. Jose, Jason H. Moore; Multilocus Analysis of Hypertension: A Hierarchical Approach. _Hum Hered 1 April 2004; 57 (1): 28–38. https://doi.org/10.1159/000077387
Download citation file:
Abstract
While hypertension is a complex disease with a well-documented genetic component, genetic studies often fail to replicate findings. One possibility for such inconsistency is that the underlying genetics of hypertension is not based on single genes of major effect, but on interactions among genes. To test this hypothesis, we studied both single locus and multilocus effects, using a case-control design of subjects from Ghana. Thirteen polymorphisms in eight candidate genes were studied. Each candidate gene has been shown to play a physiological role in blood pressure regulation and affects one of four pathways that modulate blood pressure: vasoconstriction (angiotensinogen, angiotensin converting enzyme – ACE, angiotensin II receptor), nitric oxide (NO) dependent and NO independent vasodilation pathways and sodium balance (G protein-coupled receptor kinase, GRK4). We evaluated single site allelic and genotypic associations, multilocus genotype equilibrium and multilocus genotype associations, using multifactor dimensionality reduction (MDR). For MDR, we performed systematic reanalysis of the data to address the role of various physiological pathways. We found no significant single site associations, but the hypertensive class deviated significantly from genotype equilibrium in more than 25% of all multilocus comparisons (2,162 of 8,178), whereas the normotensive class rarely did (11 of 8,178). The MDR analysis identified a two-locus model including ACE and GRK4 that successfully predicted blood pressure phenotype 70.5% of the time. Thus, our data indicate epistatic interactions play a major role in hypertension susceptibility. Our data also support a model where multiple pathways need to be affected in order to predispose to hypertension.
This content is only available via PDF.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.
Sign in
Digital Version
Pay-Per-View Access
$39.00
1 Karger Article Bundle Token
$150
Rental
This article is also available for rental through DeepDyve. 