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15 September 2007

Volume 196, Number 6
The Journal of Infectious Diseases 2007;196:826–834
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19606-0005$15.00
DOI: 10.1086/520886
MAJOR ARTICLE

Genetic Susceptibility to Respiratory Syncytial Virus Bronchiolitis Is Predominantly Associated with Innate Immune Genes

Riny Janssen,1,a

Louis Bont,4,a

Christine L. E. Siezen,1,a

Hennie M. Hodemaekers,1

Marieke J. Ermers,4

Gerda Doornbos,2

Ruben van ’t Slot,5

Ciska Wijmenga,5

Jelle J. Goeman,6

Jan L. L. Kimpen,4

Hans C. van Houwelingen,2,6

Tjeerd G. Kimman,3 and

Barbara Hoebee1

1Laboratory for Toxicology, Pathology, and Genetics, 2Expertise Centre for Methodology and Information Services, and 3Laboratory for Vaccine‐Preventable Diseases, National Institute for Public Health and the Environment, Bilthoven, 4University Medical Center, Wilhelmina Children’s Hospital, and 5Complex Genetics Section, Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, and 6Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

Background.Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in infants. Only a proportion of children infected with RSV require hospitalization. Because known risk factors for severe disease, such as premature birth, cannot fully explain differences in disease severity, genetic factors have been implicated.

Methods.To study the complexity of RSV susceptibility and to identify the genes and biological pathways involved in its development, we performed a genetic association study involving 470 children hospitalized for RSV bronchiolitis, their parents, and 1008 random, population controls. We analyzed 384 single‐nucleotide polymorphisms (SNPs) in 220 candidate genes involved in airway mucosal responses, innate immunity, chemotaxis, adaptive immunity, and allergic asthma.

Results.SNPs in the innate immune genes VDR (rs10735810; ), JUN (rs11688; ), IFNA5 (rs10757212; ), and NOS2 (rs1060826; ) demonstrated the strongest association with bronchiolitis. Apart from association at the allele level, these 4 SNPs also demonstrated association at the genotype level ( , , , and for the SNPs in VDR, JUN, IFNA5, and NOS2, respectively). The role of innate immunity as a process was reinforced by association of the whole group of innate immune SNPs when the global test for groups of genes was applied ( )

Conclusion.SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.

Received 19 March 2007; accepted 11 April 2007; electronically published 10 August 2007.

Reprints or correspondence: Dr. Riny Janssen, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, The Netherlands ().

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  • Potential conflicts of interest: none reported.

    Financial support: Dutch Asthma Foundation (grants 32.96.08 and 32.03.22).

  • R.J., L.B., and C.L.E.S. contributed equally to this work.

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