TY - JOUR T1 - Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families JF - Thorax JO - Thorax SP - 1023 LP - 1027 DO - 10.1136/thorax.55.12.1023 VL - 55 IS - 12 AU - J Hull AU - A Thomson AU - D Kwiatkowski Y1 - 2000/12/01 UR - http://thorax.bmj.com/content/55/12/1023.abstract N2 - 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-8gene 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. ER -