title: Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms.
abstract: 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.
authors.affiliation: Laboratory for Health Effects Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. B.Hoebee@rivm.nl
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoebee
authors.forename: Edwin
authors.initials: E
authors.lastname: Rietveld
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.forename: Marijke van
authors.initials: Mv
authors.lastname: Oosten
authors.forename: Hennie M
authors.initials: HM
authors.lastname: Hodemaekers
authors.forename: Nico J D
authors.initials: NJ
authors.lastname: Nagelkerke
authors.forename: Herman J
authors.initials: HJ
authors.lastname: Neijens
authors.forename: Jan L L
authors.initials: JL
authors.lastname: Kimpen
authors.forename: Tjeerd G
authors.initials: TG
authors.lastname: Kimman
mesh_terms: D001988:Bronchiolitis / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4