A Common Haplotype of Interleukin-4 Gene IL4 Is Associated with Severe Respiratory Syncytial Virus Disease in Korean Children

Respiratory syncytial virus (RSV) is a major health problem in young children, and host response to severe disease favors a Th2 immune response. To investigate the genetic basis for RSV disease severity, linked variants of 3 Th2 cytokine genes, IL4, IL13 and IL5 (which are clustered on chromosome 5q31.1) were characterized in 105 children who were hospitalized with severe RSV infection and 315 Korean control subjects in a pilot study. A common IL4 haplotype defined at 5 loci, which includes the −589T promoter variant, previously shown to be associated with increased interleukin (IL)–4 transcriptional activity and predisposition to asthma, was overrepresented in patients with severe RSV disease (odds ratio, 1.63; P=.02). These results support the hypothesis that severe RSV disease might be related to increased Th2 response, which is perhaps mediated by overexpression of IL-4, and provide preliminary evidence for a genetic link between severe RSV disease and subsequent wheezing