Association between − 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma

Background Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro. Obje...

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Bibliographic Details
Published in:Clinical and experimental allergy Vol. 29; no. 9; pp. 1204 - 1208
Main Authors: LI KAM WA, T. C, MANSUR, A. H, BRITTON, J, WILLIAMS, G, PAVORD, I, RICHARDS, K, CAMPBELL, D. A, MORTON, N, HOLGATE, S. T, MORRISON, J. F. J
Format: Journal Article
Language:English
Published: Oxford BSL Blackwell Science Ltd 01.09.1999
Blackwell
Subjects:
Adolescent
Adult
Aged
asthma
Asthma - genetics
Asthma - physiopathology
Biological and medical sciences
bronchial hyperreactivity
Bronchial Hyperreactivity - genetics
Chromosomes, Human, Pair 6
Chronic obstructive pulmonary disease, asthma
Genetic Linkage
Genetic Predisposition to Disease
genetics
Haplotypes
Histocompatibility Testing
Humans
Lymphotoxin-alpha - genetics
Medical sciences
Pneumology
Polymorphism, Genetic
Promoter Regions, Genetic
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
tumour necrosis factor
Human
Hyperreactivity
Respiratory disease
Cytokine
Bronchus
Genetic determinism
Asthma
Promoter
Gene
Tumor necrosis factor
Cohort study
Risk factor
Genetics
Obstructive pulmonary disease
Polymorphism
ISSN:0954-7894, 1365-2222
Online Access:Get full text
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Summary:Background Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro. Objective In this study we tested the hypothesis that two such polymorphisms, lymphotoxin α NcoI B*1 and − 308 TNF2 may be components of the genetic predisposition to asthma. Methods Five hundred and fifty‐six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTα NcoI locus. Results There was an association between allele two of the − 308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04–4.32, P = 0.036). However, there was no association with LTα NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR. Conclusions We conclude that the − 308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.
Bibliography:istex:29C6C90D857D1F6F87AF72B27093BD04392FE77C
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ArticleID:CEA638
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0954-7894
1365-2222
DOI:10.1046/j.1365-2222.1999.00638.x