Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.

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 interle...

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Main Authors: Hull, J, Thomson, A, Kwiatkowski, D
Format: Journal article
Language:English
Published: 2000
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author Hull, J
Thomson, A
Kwiatkowski, D
author_facet Hull, J
Thomson, A
Kwiatkowski, D
author_sort Hull, J
collection OXFORD
description 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. METHODS: Common 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. RESULTS: A 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). CONCLUSION: Disease 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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spelling oxford-uuid:00f0c03e-0876-4902-bc1c-a7a5509fba4b2022-03-26T08:32:09ZAssociation of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:00f0c03e-0876-4902-bc1c-a7a5509fba4bEnglishSymplectic Elements at Oxford2000Hull, JThomson, AKwiatkowski, DBACKGROUND: 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. METHODS: Common 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. RESULTS: A 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). CONCLUSION: Disease 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.
spellingShingle Hull, J
Thomson, A
Kwiatkowski, D
Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title_full Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title_fullStr Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title_full_unstemmed Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title_short Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.
title_sort association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in uk families
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AT kwiatkowskid associationofrespiratorysyncytialvirusbronchiolitiswiththeinterleukin8generegioninukfamilies