Thorax

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER


[Advanced]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moffatt, M. F
Right arrow Articles by Cookson, W. O C M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moffatt, M. F
Right arrow Articles by Cookson, W. O C M
Thorax 1999;54:757-761 ( September )

Extended tumour necrosis factor/HLA-DR haplotypes and asthma in an Australian population sample

Miriam F Moffatta, Alan Jamesb, Gerard Ryanb, A William Muskb, William O C M Cooksona

a Asthma Genetics Group, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK, b Department of Respiratory Medicine & Busselton Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia 6009

Correspondence to: Dr M F Moffatt.

Received 8 January 1999; Returned to authors 10 March 1999; Revised version received 26 April 1999; Accepted for publication 20 May 1999

BACKGROUND---Tumour necrosis factor (TNF) is a potent pro-inflammatory cytokine which is prominent in asthmatic airways. TNF shows genetic variations in secretion which are linked to polymorphisms in the TNF gene complex and the surrounding major histocompatibility (MHC) locus. These polymorphisms do not seem to be themselves functionally important. In these circumstances, the identification of disease associated haplotypes (combination of alleles on individual chromosomes) may narrow the search for polymorphisms which alter gene function.
METHODS---TNF-308, LTalpha NcoI, and HLA-DRB1 polymorphisms were investigated for association with asthma, bronchial responsiveness, and medication use in 1004 subjects in 230 families from a general population sample.
RESULTS---The common LTalpha NcoI*1/TNF-308*2/HLA-DRB1*03 haplotype, which was present in 11% of unrelated individuals, was weakly associated with asthma (OR = 1.38, p = 0.016, corrected for familial correlation). The rarer LTalpha NcoI*1/TNF-308*2/HLA-DRB1*02 haplotype, which was found in 0.6% of unrelated subjects, was more strongly associated with asthma (OR = 6.68, p = 0.002). This haplotype also showed association with bronchial hyperresponsiveness (OR = 21.9, p = 0.0000) and the use of inhaled or oral steroids (OR 8.0, p = 0.04).
CONCLUSIONS---The results of this study show only two extended TNF/HLA-DR haplotypes to be associated with asthma. The search for functional alleles responsible for an increased risk of asthma should concentrate on the LTalpha NcoI*1/TNF-308*2/HLA-DRB1*02 haplotype.


Keywords: asthma; genetics; tumour necrosis factor; TNF/HLA-DR haplotypes

© 1999 by Thorax


This article has been cited by other articles:


Home page
 Eur Respir JHome page
F. Castro-Giner, M. Kogevinas, M. Machler, R. de Cid, K. Van Steen, M. Imboden, C. Schindler, W. Berger, J. R. Gonzalez, K. A. Franklin, et al.
TNFA -308G>A in two international population-based cohorts and risk of asthma
Eur. Respir. J., August 1, 2008; 32(2): 350 - 361.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. A. Beuther, S. T. Weiss, and E. R. Sutherland
Obesity and Asthma
Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 112 - 119.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
J Gao, G Shan, B Sun, P J Thompson, and X Gao
Association between polymorphism of tumour necrosis factor {alpha}-308 gene promoter and asthma: a meta-analysis
Thorax, June 1, 2006; 61(6): 466 - 471.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Y.-F. Li, W. J. Gauderman, E. Avol, L. Dubeau, and F. D. Gilliland
Associations of Tumor Necrosis Factor G-308A with Childhood Asthma and Wheezing
Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 970 - 976.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
H. Bilolikar, A. R. Nam, M. Rosenthal, J. C. Davies, D. C. Henderson, and I. M. Balfour-Lynn
Tumour necrosis factor gene polymorphisms and childhood wheezing
Eur. Respir. J., October 1, 2005; 26(4): 637 - 646.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. G. Randolph, C. Lange, E. K. Silverman, R. Lazarus, and S. T. Weiss
Extended Haplotype in the Tumor Necrosis Factor Gene Cluster Is Associated with Asthma and Asthma-related Phenotypes
Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 687 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. F. Moffatt, J. A. Faux, S. Lester, P. Pare, J. McCluskey, R. Spargo, A. James, A. W. Musk, and W. O. C. M. Cookson
Atopy, respiratory function and HLA-DR in Aboriginal Australians
Hum. Mol. Genet., March 15, 2003; 12(6): 625 - 630.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
G. Woszczek, M.L. Kowalski, and M. Borowiec
Association of asthma and total IgE levels with human leucocyte antigen-DR in patients with grass allergy
Eur. Respir. J., July 1, 2002; 20(1): 79 - 85.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
K G Tantisira and S T Weiss
Complex interactions in complex traits: obesity and asthma
Thorax, September 1, 2001; 56(90002): ii64 - 74.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 1999 BMJ Publishing Group Ltd & British Thoracic Society