Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms

J Infect Dis. 2003 Jan 1;187(1):2-11. doi: 10.1086/345859. Epub 2002 Dec 13.


The association of variants of genes encoding interleukin (IL)-4 and the IL-4 receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C-590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment-length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study). Results were also analyzed in a combination of these 2 tests, using Fisher's method. The IL-4 590T allele was found more frequently among children hospitalized with RSV than expected in the case-control (odds ratio [OR], 1.43; P=.04) and combination (OR, 1.41; P=.02) tests. Among children who were >6 months old when they were hospitalized, compared with the control group or with the <6 months old who were hospitalized for RSV infection, higher frequencies of both the IL-4 590T allele and the IL-4Ralpha R551 allele were found. These results indicate that gain-of-function variants of T helper type 2 cytokine genes may play a role in increasing the severity of RSV disease, which appears more pronounced after the first half-year of life.

MeSH terms

  • Bronchiolitis / genetics
  • Bronchiolitis / immunology*
  • Case-Control Studies
  • Chromosome Mapping
  • Female
  • Humans
  • Infant
  • Interleukin-13 / genetics
  • Interleukin-4 / genetics*
  • Male
  • Polymorphism, Genetic
  • Receptors, Interleukin-4 / genetics*
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Th2 Cells / immunology


  • Interleukin-13
  • Receptors, Interleukin-4
  • Interleukin-4