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University
Department of Paediatrics, Level 4, John Radcliffe Hospital, Oxford
OX3 9DU
Correspondence to: Dr J Hull jhull{at}molbiol.ox.ac.uk
Received 3 April 2000; Returned to authors 8 August 2000; Revised version received 22 August 2000; Accepted for publication 14 September 2000
BACKGROUND
Respiratory
syncytial virus (RSV) infects nearly all children by the end of their
second winter. Why some develop bronchiolitis is poorly understood; it
is not known whether there is a genetic component. The pathological
features include neutrophil infiltration and high levels of interleukin
8 (IL-8), a potent neutrophil chemoattractant.
METHODSCommon genetic
variants of the promoter region of the IL-8
gene were identified by sequencing DNA from 36 healthy individuals. Genetic correlates of IL-8 production were assessed using whole blood
from 50 healthy subjects. To investigate genetic correlates of disease
severity 117 nuclear families were recruited in which a child had
required hospital admission for RSV bronchiolitis.
RESULTSA common
single nucleotide polymorphism (allele frequency 0.44) was identified
251 bp upstream of the IL-8 transcription
start site. The IL8-251A allele tended to be associated with increased IL-8 production by lipopolysaccharide stimulated whole blood (p=0.07). Using the transmission disequilibrium test, the frequency of this allele was significantly increased in infants with bronchiolitis (transmission = 62% (95% confidence interval (CI) 53 to 71), p=0.014) and particularly in those without known risk factors (transmission = 78% (95% CI 62 to 93), p=0.004).
CONCLUSIONDisease
severity following RSV infection appears to be determined by a genetic
factor close to the IL-8 gene. Further
analysis of this effect may elucidate causal processes in the
pathogenesis of RSV bronchiolitis.
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