Human Molecular Genetics, Vol 6, 551-554, Copyright © 1997 by Oxford University Press
MF Moffatt and WO Cookson
Airway inflammation is a prominent feature of asthma. The pro- inflammatory
cytokine Tumour Necrosis Factor shows constitutional variation in its level
of secretion, which is linked to polymorphisms within the TNF gene complex
and the surrounding MHC. In this study, 413 subjects in 88 nuclear families
from a general population sample were examined for association with asthma
and TNF polymorphisms. Ninety-two subjects were asthmatic, as defined by
questionnaire. Asthma was significantly more common in subjects with allele
1 of the LT alpha NcoI polymorphism (LT alpha NcoI*1) (p = 0.005), and
allele 2 of the TNF-308 polymorphism (TNF-308*2) (p = 0.004). The
association was confined to the LT alpha NcoI*1/TNF-308*2 haplotype, so
that it was not possible to differentiate between the effects of LT alpha
NcoI and TNF- 308 alleles. The HLA-DR locus was excluded as a cause of this
association. The results suggest that genetic influences on inflammation
may be important in the pathogenesis of asthma.
ARTICLES
Tumour necrosis factor haplotypes and asthma
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
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