Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children

Morahan, Grant, Huang, Dexing, Wu, Mark, Holt, Barbara J., White, Gregory P., Kendall, Garth E., Sly, Prof Peter D. and Holt, Patrick G. (2002) Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children. Lancet, 360 9331: 455-459. doi:10.1016/S0140-6736(02)09676-9

Author Morahan, Grant
Huang, Dexing
Wu, Mark
Holt, Barbara J.
White, Gregory P.
Kendall, Garth E.
Sly, Prof Peter D.
Holt, Patrick G.
Title Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
Publication date 2002-08-01
Year available 2002
Sub-type Article (original research)
DOI 10.1016/S0140-6736(02)09676-9
Open Access Status Not Open Access
Volume 360
Issue 9331
Start page 455
End page 459
Total pages 5
Place of publication London, United Kingdom
Publisher The Lancet Publishing Group
Language eng
Abstract Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms.
Formatted abstract
Background: Severe asthma is a frequent cause of hospital admission, especially among children. The main environmental triggers of airway inflammation in asthma are viruses and aeroallergens. These agents elicit reciprocal immune responses, characterised by production of T helper 1 and T helper 2 cytokines, respectively. There is no genetic explanation for how hyper-responsiveness to these disparate environmental stimuli develops among individuals with asthma. Our aim was to assess relation between an IL12B promoter polymorphism and asthma.

Methods: We did a cohort study in which we initially genotyped 411 6-year olds for the IL12B promoter polymorphism. We then assessed the relation between this polymorphism and asthma severity. A further 85 asthmatic children in an additional sample of 433 children from the same cohort were then assessed to confirm these findings. We also examined in-vitro interleukin-12 responses in a subgroup of individuals.

Findings: Heterozygosity for the IL12B promoter polymorphism was observed in 76% (16) of atopic and non-atopic individuals with severe asthma in the initial sample. By comparison, heterozygotes comprised only 31% (17) of the moderate asthma group, and 48% (20) of individuals with mild asthma were heterozygous, as were unaffected controls. These findings were confirmed in the second sample (overall p<0.0001). Our data suggest that IL12B promoter heterozygosity contributes to asthma severity rather than susceptibility per se. The severity-predisposing genotype was associated with reduced interleukin 12 p40 gene transcription and decreased interleukin 12 p70 secretion.

Interpretation: Interleukin 12 plays a key part in antagonism of T helper 2 differentiation, and in induction of antiviral host defense. Genetically determined attenuation of interleukin-12 response capacity would, therefore, provide a plausible common immunological pathway to disease severity for the two major forms of asthma.
Keyword Asthma
basophil activation
regulatory T cells
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID G0601361
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
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Created: Wed, 17 Nov 2010, 21:39:39 EST