Evidence for a Major Gene Influence on Tumor Necrosis Factor-α Expression in Tuberculosis: Path and Segregation AnalysisStein C.M.a-c · Nshuti L.b, d · Chiunda A.B.a, b · Boom W.H.b · Elston R.C.a · Mugerwa R.D.b, d · Iyengar S.K.a · Whalen C.C.a-c
aDepartment of Epidemiology and Biostatistics, bTuberculosis Research Unit, and cCenter for Modern Epidemiology of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, USA; dClinical Epidemiology Unit, Makerere University School of Medicine, Kampala, Uganda
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Objective: Tuberculosis (TB) is a growing global public health problem. Several studies suggest a role for host genetics in disease susceptibility, but studies to date have been inconsistent and a comprehensive genetic model has not emerged. A limitation of previous genetic studies is that they only analyzed the binary trait TB, which does not reflect disease heterogeneity. Furthermore, these studies have not accounted for the influence of shared environment within households on TB risk, which may spuriously inflate estimates of heritability. Methods: We conducted a household contact study in a TB-endemic community in Uganda. Antigen-induced tumor necrosis factor-α (TNFα) expression, a key component of the underlying immune response to TB, was used as an endophenotype for TB. Results: Path analysis, conducted to assess the effect of shared environment, suggested that TNFα is heritable (narrow sense heritability = 34–66%); the effect of shared environment is minimal (1–14%), but gene-environment interaction may be involved. Segregation analysis of TNFα suggested a major gene model that explained one-third of the phenotypic variance, and provided putative evidence of natural selection acting on this phenotype. Conclusion: Our data further support TNFα as an endophenotype for TB, as it may increase power to detect disease-predisposing loci.
© 2005 S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: 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.