TY - JOUR
T1 - Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes
AU - Janssen, Riny
AU - Bont, Louis
AU - Siezen, Christine L.E.
AU - Hodemaekers, Hennie M.
AU - Ermers, Marieke J.
AU - Doornbos, Gerda
AU - Van 'T Slot, Ruben
AU - Wijmenga, Ciska
AU - Goeman, Jelle J.
AU - Kimpen, Jan L.L.
AU - Van Houwelingen, Hans C.
AU - Kimman, Tjeerd G.
AU - Hoebee, Barbara
N1 - Funding Information:
Received 19 March 2007; accepted 11 April 2007; electronically published 10 August 2007. Potential conflicts of interest: none reported. Financial support: Dutch Asthma Foundation (grants 32.96.08 and 32.03.22). a R.J., L.B., and C.L.E.S. contributed equally to this work. 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 ([email protected]).
PY - 2007/9/15
Y1 - 2007/9/15
N2 - 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; P = .0017), JUN (rs1 1688; P = .0093), IFNA5 (rs10757212; P = .0093), and NOS2 (rs1060826; P = .0031) demonstrated the strongest association with bronchiolitis. Apart from association at the allele level, these 4 SNPs also demonstrated association at the genotype level (P = .0056, P = .0285, P = .0372, and P = .0117 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 (P = .046) Conclusion. SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.
AB - 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; P = .0017), JUN (rs1 1688; P = .0093), IFNA5 (rs10757212; P = .0093), and NOS2 (rs1060826; P = .0031) demonstrated the strongest association with bronchiolitis. Apart from association at the allele level, these 4 SNPs also demonstrated association at the genotype level (P = .0056, P = .0285, P = .0372, and P = .0117 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 (P = .046) Conclusion. SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.
UR - https://www.scopus.com/pages/publications/34548475750
U2 - 10.1086/520886
DO - 10.1086/520886
M3 - Article
C2 - 17703412
AN - SCOPUS:34548475750
SN - 1537-6613
VL - 196
SP - 826
EP - 834
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 6
ER -